INSULIN INITIATION AND INTENSIFICATION WITH A FOCUS ON HYPOGLYCEMIA REDUCTION Jaiwant Rangi, MD, FACE Nov 10 th 2018
DISCLOSURES Speaker Novo Nordisk Sanofi-Aventis Boheringer Ingleheim Merck Abbvie Abbott
T1DM: DESTRUCTION OF THE PANCREAS Type 1 Diabetes is caused by the autoimmune destruction of insulin producing ß-cells Antigen TCR T Cell T Cell ß-cells T-cells mediated killing of ß-cells
T2DM: RESISTANCE TO INSULIN Food Intake Fat cells Muscle cells Liver Carbohydrate absorbed Insulin Elevated Blood Glucose Pancreas
INSULIN ACTION Glucose uptake Lipolysis Fat storage Fat cells Muscle cells Liver Glucose production Glucose storage Carbohydrate absorbed Insulin Elevated Blood Glucose Pancreas
INSULIN RESISTANCE Fat cells Muscle cells Liver Carbohydrate absorbed Insulin Elevated Blood Glucose Pancreas
CASE #1 48 year old man with Type 2 DM x 12 years. Current DM meds Metformin 1000 mg BID Sitagliptin 100 mg QD Glipizide 10 mg BID On ACE-I for Hypertension and Statin for elevated Cholesterol
CASE #1 PE: Obese, 5 10, 245 lbs. BMI 35.15 PE otherwise unremarkable HbA1C 8.7 % Fasting BG levels between 160-190 What is the next step for DM management?
BARRIERS TO STARTING INSULIN Fear of needles Fear of hypoglycemia No time to learn about insulin Concerns about side effects of insulin History of family member that was on insulin and then Feeling like failure in terms of diabetes
INSULIN DELIVERY DEVICES
STARTING BASAL INSULIN AACE Guidelines: Pick a starting dose for basal insulin A1c < 8 % 14-28 units A1c > 8 % 28-43 units I often start at either 10 or 20 units or based on weight for morbidly obese patients otherwise it takes long to titrate
STARTING BASAL INSULIN Titration: Increase insulin by 2 units 2 x per week (pick days) until fasting blood glucose levels are to goal Decrease by 2 units if hypoglycemia Goal Blood Sugar: Generally 90-130 mg/dl Higher risk of hypoglycemia 100-150 mg/dl Max dose insulin: 40 units is a reasonable start Allows patients to be comfortable increasing dose
STARTING BASAL INSULIN Start insulin Glargine 20 units between 9-11 PM Check FSBG levels every morning Goal fasting BG: 90-130 mg/dl Every Wed and Sat review your blood glucose levels and if not to goal, increase Glargine dose by 2 units (example increase from 20 to 22 units daily) Once you reach Glargine 40 units please contact provider
CASE #1 CONT. Started on Glargine 20 units Goal fasting BG 90-130 mg/dl Titrate 2 x per week Follow up appointment in 1 month Glargine increased to 32 units Fasting BG usually around 130-140 mg/dl Had one episode of low BG with symptoms, checked FSBG and it was 82 mg/dl Stopped increasing his dose after that low
CASE #2 82 year old man with Type 2 Diabetes for 30 years. He lives by himself and is very worried about low blood glucose levels Current DM meds: Metformin 1000 mg BID Degludec 24 units at night Empagliflozin 10 mg QD HbA1c of 8.4 % at appointment today. Checks FSBG once per day. Fasting range 98-164 mg/dl What are your options for next steps?
CASE #2 Options include: GLP1-RA SU Prandial Insulin DPP4 inhibitor TZD If hypoglycemia is his main concern, what options would you consider?
CASE #2 CONT. Decided to start on a GLP1 RA Options: Once daily injection (Liraglutide/Victoza) Once weekly injection (Duglaglutide / Trulicity, Exenatide/Bydureon, Semaglutide / Ozempic) Combination (Soliqua 100/33 Glargine and Lixisenatide or Xultrophy 100/3.6 Degludec and Liraglutide)
CASE #3 62 year old woman with a history type 2 DM for 14 years She struggles with her diet and finds the higher carbohydrate options easiest while at work Current DM meds: Toujeo (U300 Glargine) 56 units Dulaglitide/Trulicity 1.5 mg weekly Canagliflozin / Invokana 300 mg QD Repaglinide / Prandin 1 mg 1-2 tabs before meals
Case #3 cont. HbA1c 10.0 %!! Forgot her BG meter, but does try to check her FSBG 1-2 times per week fasting Reports good BG levels, usually around 100-120 mg/dl in the morning Admits, she does miss the Repaglinide / Prandin several times per week
Case #3 cont. CGM placed and she returns in 2 weeks with data
INSULIN OPTIONS
BASAL / BOLUS INSULIN
BASAL/BOLUS INSULIN Basal Insulin Long acting insulin to help lower fasting and between meal BG levels Bolus Insulin Prandial Insulin (meal time) Short acting insulin taken before a meal to prevent a post prandial spike Correctional Insulin Short acting insulin, extra insulin taken to correct a high BG level
CASE #3 CONT. Will start short acting insulin prior to each meal Current Basal insulin dose is 54 units. But her BG is dropping 100-200 mg/dl overnight Decrease Basal Insulin to 40 units Start prandial insulin with meal(s)
CASE #3 Basal plus one: Start 10 % of basal or 5 units with one meals Basal / Bolus: Start 50 % basal and 50 % bolus Total daily insulin dose: 0.3-0.5 units/kg
CASE #3 CONT Decrease Toujeo dose to 40 units Start Lispro 10 units with each meal Encouraged her to keep CHO consistent around 45-60 gm. per meal Add correction insulin if BG above 150 per sliding scale
CASE #3 CONT. Blood Sugar: Insulin Dose: <70 No insulin, 15 gm of CHO and repeat 70-150 10 units 151-200 12 units 201-250 14 units 251-300 16 units >300 18 units
CASE #3 She does not like carrying her Sliding Scale around, how else can she determine her insulin doses? CHO counting working with a dietician, patient learns to count CHO and determine insulin dose based on CHO content of the meal example: 1 unit of insulin per 5 gm. of CHO Correction or sensitivity factor determine decrease in BG per unit of insulin example: 1 unit per 25 mg/dl above target of 150 mg/dl
CASE #4 67 year old man with Type 2 DM x 22 years presents to your office. His complications include nephropathy and neuropathy Rx History: He has been on insulin for over 15 years. No oral agents due to renal disease and intolerance Current RX: Glargine 80 units Lispro 25 units with meals
CONCENTRATED INSULIN Is he a good candidate for a concentrated insulin? What options are available for concentrated Insulin's?
CONCENTRATED INSULIN Candidates: Insulin resistance: on medications such as steroids Genetic forms of insulin resistance On more than 100 units per day of insulin Presence of insulin antibodies Type 1 DM with obesity or overweight
CONCENTRATED INSULIN OPTIONS U500 syringe and vial remember dose is 5 X amount seen on the insulin syringe U500 Pen dose is in units U300 Glargine (Toujeo) Solostar pen U200 Degludec (Tresiba) - Flexpen U200 Lispro (Humalog) Kwik pen
INTEGRATED PUMP/CGM SYSTEMS Minimum 670G is the first hybrid closed loop system Data from the CGM is transmitted to the pump and the basal rate is adjusted Patient must still enter CHO and corrections More integrated systems to come in the next 1-2 years
CASE #4 CONT. Started on U-300 Glargine and U-200 Humalog with meals Advantages: Smaller injection volume (more comfortable) Pens last longer (and less waste) Potentially less risk of hypoglycemia (especially overnight) Less time dependent (any time of day dosing)
CASE #5 24 year old woman with Type 1 Diabetes working at a start up just moved to the area DM diagnosed at age 9. No complications HbA1c 8.2 % Current insulin doses: Degludec: 12 units AM, 8 units PM Lispro: 1 unit per 14 gm of carbohydrate 1 unit per 20 mg/dl above target of 120 mg/dl She is interested in learning more about technology for Diabetes what are her options?
TECHNOLOGY Insulin Delivery Systems Blood glucose monitoring Meters Continuous Glucose Sensors
CONTINUOUS SUBCUTANEOUS INSULIN INFUSION (CSII) Catheter is placed subcutaneously and connected to an electronic pump. Pump delivers low levels of basal rate short acting insulin (rates can vary during the day). Patient can give boluses for meals and corrections for high blood glucose levels.
REAL TIME CONTINUOUS GLUCOSE SENSORS Subcutaneous catheter inserted every 7-10 days. Interstitial fluid BG measurement every 5 minutes. Alarms can be set for highs and lows. Currently available CGMs: Medtronic Minimed Dexcom G5 (G6 any day now) Abbott Freestyle Libre
REAL TIME CONTINUOUS GLUCOSE SENSORS
CASE #5 CONT. Patients decides to start on a CGM to help warn her about hypoglycemia Finds that she was having nocturnal hypoglycemia and rebound fasting high BG levels Decreased her Basal Insulin Discovered a lot of after meal highs, needs to adjust the timing of her meal time insulin She is considering her options for a closed loop system in the future
Thank you! Contact information: email: Jaiwantrangi@hotmail.com Office: 530-677-0700