Basics of Continuous Subcutaneous Insulin Infusion Therapy. Lubna Mirza, MD Norman Endocrinology Associates PDF Free Download

Basics of Continuous Subcutaneous Insulin Infusion Therapy Lubna Mirza, MD Norman Endocrinology Associates 2018

Preamble Roughly 20% - 30% of patients with T1DM and fewer than 1% of insulin-treated patients with T2DM use an insulin pump In 2007, the US FDA estimated that the number of patients with T1DM using CSII was ~375,000 By 2050, up to one-third of US residents may have T2DM; many of these individuals will be insulinrequiring Therefore, more clinicians must develop a comprehensive understanding of these devices HSBC Global Research. Healthcare US Equipment & Supplies. 2005. U.S. FDA. General Hospital and Personal Use Medical Devices Panel. 2010 U.S. CDC. CDC Media Relations - Press Release: October 22, 2010. T1DM: type 1 diabetes mellitus T2DM: type 2 diabetes mellitus FDA: U.S. Food and Drug Administration CSII: continuous subcutaneous insulin infusion

History of insulin pumps Outline Benefits of improved glycemic control Advantages of insulin pump therapy Inpatient Insulin pump management Carbohydrate Counting Hypoglycemia and hyperglycemia prevention Conclusions

Best and Banting

Evolution of Diabetes Management Technologies Insulin Pump Therapy Glucose Sensors BG Meters Urine Test Strips Urine Tasting 1776 Discovery of Insulin 1900s 1921 1977 1978 1999 Artificial Pancreas

First Insulin Pump (1963 by Dr. Arnold Kadish)

Early Insulin Pumps

Insulin Pumps

Insulin Pumps on the Market Accu-Chek Combo System Asante Snap Insulin Pump System MiniMed Paradigm Real-Time Revel System (523/723) MiniMed 530G with Enlite (551/751) OmniPod Insulin Management System OneTouch Ping t:slim Insulin Pump V-Go Disposable Insulin Delivery Device Roche Health Solutions Asante Solutions Medtronic MiniMed Medtronic MiniMed Insulet Corporation Animas Tandem Diabetes Care Valeritas, Inc.

U.S. Pump Usage Total Patients Using Insulin Pumps 200,000 157,000 150,000 120,000 100,000 81,000 60,000 50,000 6,600 8,700 11,400 15,000 20,000 43,000 35,000 26,500 0 '90 '91 '92 '93 '94 '95 '96 '97 '98 '99 2000 2001 2002

How Diabetes Specialists Treat Their Own Type 1 Diabetes AADE Membership n=229 60% ADA Membership n=293 52% Color Key: Pump Therapy General Type 1 Population* 6% Injections Industry estimates at time of survey (9/98); Graff: Diabetes Educator 2000; 46:460-467

Outline History of insulin pumps Benefits of improved glycemic control Advantages of insulin pump therapy Inpatient Insulin pump management Carbohydrate Counting Hypoglycemia and hyperglycemia prevention Conclusions

RISK Potential Chronic Complications of Elevated HbA1c Microalbuminuria Mild Retinopathy Mild Neuropathy Foot Ulcers Angina Heart Attack Coronary Bypass Surgery Stroke Blindness Albuminuria Amputation Macular Edema Dialysis Proliferative Kidney Retinopathy Transplant Peridontal Disease Impotence Gastroparesis Depression Good CONTROL Poor

DCCT Microvascular Risk Reduction With Intensive Treatment Complication Reduction in Relative Risk Retinopathy 63% Nephropathy 54% Neuropathy 60% Data from the Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329:977-986.

Treatment Strategies for Diabetes: Are Patients Achieving Good Control? Hypertension Hyperlipidemia Glycemic control BP <140/90 mm Hg LDL-C <130 mg/dl A1C <7.0 41% 41% 42% 59% 59% 58% Controlled Uncontrolled Harris MI et al. Diabetes Care. 2000;23:754

The Goal of Insulin Therapy: Attempt to Mimic Normal Pancreatic Function PLASMA GLUCOSE mg/dl PLASMA FREE INSULIN u/ml 160 140 120 100 80 60 75 60 40 30 15 Schade, Skyler, Santiago, Rizza, Intensive Insulin Therapy, 1993, p. 131. 0 330 B L S HS 1130 1530 1930 HOURS 2330 0330 0730

Insulin Effect Twice-daily Split-mixed Regimens Regular NPH B L S HS B 6-23

Insulin Effect Basal Bolus Regimen with Glargine and Lispro lispro Glargine B L S HS B 6-56

Insulin Effect Continuous Subcutaneous Insulin Infusion Bolus Basal B L S HS B

Pharmacokinetics of CSII vs MDI Uses immediate acting insulin More predictable absorption Uses one injection site Reduces variations in absorption Eliminates most of the subcutaneous insulin depot Closest match with physiologic needs * Lauritzen: Diabetologia 1983; 24:326-9

Type 1 Diabetes A 2010 Cochrane review compared the use of CSII vs. MDI insulin regimens (23 randomized studies involving 976 patients with T1DM) A significant difference was documented in HbA 1c response, favoring CSII CSII users demonstrated greater improvements in quality of life measures Severe hypoglycemia appeared to be reduced in CSII users Misso ML, et al. Cochrane Database Syst Rev. 2010;(1):CD005103. doi(1):cd005103 CSII: continuous subcutaneous insulin infusion MDI: multiple daily injection T1DM: type 1 diabetes mellitus

Type 1 Diabetes The STAR-3 study showed significantly greater HbA 1c reductions in patients with T1DM randomly assigned to sensor-augmented insulin pump therapy vs. MDI A higher proportion of patients randomly assigned to pump therapy achieved an HbA 1c <7% without any increase in severe hypoglycemia rates or weight gain vs. the MDI group Based on currently available data, CSII is justified for basal-bolus insulin therapy in patients with T1DM Bergenstal RM, et al. N Engl J Med. 2010;363(4):311-320 STAR-3: Sensor-Augmented Pump Therapy for A1C Reduction T1DM: type 1 diabetes mellitus MDI: multiple daily injection CSII: continuous subcutaneous insulin infusion

Trial Evidence: CSII versus MDI use in Population: Comparison of glycemic control in 58 patients while on MDI x 3yrs and subsequent CSII x 3yrs Methods: Mean HbA1c% routine clinical practice Retrospective, observational cohort study of patients with Type 1 diabetes 10 9 8 7 6 8.4 P=0.001 7.7 9.2 P=0.0006 8.2 10.0 P=0.0006 8.4 MDI CSII Bell and Ovalle, Endocr Pract 2000;6:357-60 Entire Cohort MDI HbA1c >8.0% MDI HbA1c >9.0%

Improved Control and Less Variability Glucose (mg/dl) 400 Pump Therapy With Pump Therapy Finger Stick Sensor Multiple Daily Injections Glucose (mg/dl) 400 Finger Stick Sensor 350 300 250 200 150 100 50 0 12:00 a.m.6:00 a.m. 12:00 p.m.6:00 p.m. 12:00 a.m. Time (Day) 350 300 250 200 150 100 50 0 12:00 a.m.6:00 a.m. 12:00 p.m.6:00 p.m. 12:00 a.m. Time (Day)

Improved Control: Decreased Hypoglycemia 150 138 Episodes per 100 pt yrs 100 50 22 26 39 36 N=55 0 Pre CSII 1 yr 2 yr 3 yr 4 yr ------------ With CSII------------ Bode et al: Diabetes Care 1996; 19:324-7

(episodes / 100 pt years) Diabetic Ketoacidosis 16 14 12 10 8 6 4 2 0 15 Pre-CSII 7 Post-CSII Bode, BW, Diabetes Care 19:324-7, 1996.

Pediatric Patients Pediatric diabetes specialists agree that CSII is indicated for pediatric patients with: Elevated HbA 1c levels on injection therapy Frequent, severe hypoglycemia Widely fluctuating glucose levels A treatment regimen that compromises lifestyle Microvascular complications and/or microvascular risk factors Ideal pediatric candidates have motivated families, with a working understanding of diabetes management, and committed to monitoring blood glucose 4 times/day Patient age and duration of diabetes should not be factors in determining the transition from injections to CSII Phillip M, et al. Diabetes Care. 2007;30(6):1653-1662 CSII: continuous subcutaneous insulin infusion

Challenges of Pump Therapy Learning curve Risk of DKA Possible weight gain Frequent monitoring required Potential site infections Inconvenience in wearing pump Education and follow-up required Cost

Advantages of Pump Therapy- Summary Improved blood glucose control Improved AIC s Decreased hypoglycemia and hyperglycemia Delay in incidence and progression of complications Precise dosage delivery Improved control for pre-conception and pregnancy Management of dawn phenomenon Increased flexibility in lifestyle Improved control during exercise Improved gastroparesis management

Insulin Pumps in Inpatient Settings When Insulin pump users are evaluated for a non-acute hyper- or hypoglycemic crisis, they typically have more insulin pump knowledge and expertise than the medical professionals handling their hospital stay At emergency room or hospital admission, the specialist(s) responsible for the patient s ambulatory pump management should be contacted promptly to make decisions about infusion adjustments Patients should be instructed to not discontinue the pump infusion, unless directed by their diabetes specialist CSII: continuous subcutaneous insulin infusion

Key Components of Insulin Pump Settings Basal Rate: Rate at which rapid acting insulin is delivered as a continuous subcutaneous flow Expressed as units/ hour. The patient may have multiple basal rates programmed during the 24 hour period. Carb Ratio: The predicted amount of insulin needed per gram of carbohydrate for a specific meal or snack. (e.g., 1 unit insulin needed for10 grams of carbohydrate) Correction factor/ Sensitivity factor: The amount that blood glucose (mg/dl or mmol/l) will be reduced by 1 unit of insulin. (e.g a correction factor of 50 means that 1 unit of insulin will reduce BG by 50 mg/dl)

Determine Competency To Continue Insulin Pump Inpatient Can open the management menu of the device Are able to adjust the basal rate Are able to adjust the bolus dose Can demonstrate technical competency Can undertake appropriate problem solving actions if blood sugars are high or low Have adequate supplies of infusion sets, spare batteries and the insulin vials Have been performing regular blood glucose monitoring tests

Contraindications for using Insulin Pump Inpatient Patients with an impaired level of consciousness Patients with critical illness requiring intensive care Patients with major psychiatric disturbance Diabetic ketoacidosis Patients refusing or unwilling to participate in self care Lack of infusion sets, spare batteries and other equipment required to maintain patient on CSII therapy

Documentation It must be clearly written in the medical record that the patient is on an insulin pump The brand name and model of the pump must be written in the medical record The type of insulin used in the insulin pump must be identified and recorded in the blood glucose monitoring form The current basal and bolus insulin doses must be documented in the medical record Ideally the pump data would be downloaded and the print out stored in the medical chart

Medtronic Pump Download

Practice Question A 63 year-old man is evaluated during a follow-up visit for management of type 1 diabetes mellitus. He was diagnosed at 18 years of age and has multiple chronic complications from his diabetes, including end-stage kidney disease requiring hemodialysis, gastroparesis, frequent hypoglycemia with hypoglycemic unawareness, painful peripheral neuropathy, and proliferative retinopathy. The patient uses an insulin pump and a continuous glucose monitoring system to manage his diabetes. He is adherent with his regimen and performs multiple fingerstick blood glucose measurements with values ranging from 65 to 250 mg/dl (3.6-13.9 mmol/l). His most recent hemoglobin A1c level is 7.5%

Which of the following is the most appropriate next step in the management of this patient? (a) Alter insulin pump settings to attain a hemoglobin A1c goal of less than 7.0% (b) Alter insulin pump settings to decrease the insulin doses (c) Discontinue the insulin pump, start subcutaneous insulin injections (d) Start gabapentin for the treatment of painful peripheral neuropathy

(b) Alter insulin pump settings to decrease the insulin doses KEYPOINT A less stringent hemoglobin A1c goal is appropriate for persons with diabetes mellitus with a decreased life expectancy, history of severe hypoglycemia, multiple comorbidities, or advanced microvascular or macrovascular disease

Consultations Endocrinologist or Physician with interest in diabetes Diabetes Educator or diabetes resource person trained in insulin pump management Dietitian

Monitor BG Monitoring Fasting in the morning Pre-meals Bedtime Assess basal insulin dose by fasting and premeal BG s Adjust nighttime basal based on pre-breakfast BG Adjust basal rate by 10% to avoid over-correction

Healthcare Across Borders CGM Benefits Increased sense of security Immediate feedback look and learn Improves control when used Worth out of pocket cost for many One unit available for about a Starbucks a day Reimbursement gradually catching on

Do You Need to Remove Pump? Any radiological investigation (pump must be removed) CT Scan (pump must be removed) MRI scan (pump must be removed, including metal cannula) Physiotherapy (depending on the therapy) Hydrotherapy (even if the pump is labeled as water-proof)

Specific Scenarios 63 year old type 2 diabetic patient scheduled for cardiac angiogram. NPO after midnight 21 year old type 1 diabetic woman getting parathyroidectomy the next day. NPO after midnight 40 year old woman with type 1 diabetes admitted for Pneumonia 36 year old man with type 1 diabetes in DKA 55 year old man with type 1 diabetes getting colonoscopy

Pre-meal boluses: Bolus Dose Insulin Taken before meals Covers mealtime carbohydrate intake Prevents postprandial hyperglycemia Correction or supplementation boluses: Used to Correct and treat hyperglycemia May be given alone between meals for hyperglycemia May be given to supplement already scheduled insulin to cover pre-meal hyperglycemia

Why Count Carbs? It works Increases flexibility in food choices and the amounts of foods consumed Easy to understand Well-accepted

Macronutrient Conversion to Blood Glucose

Carbohydrate Counting Benefits Allows for variation in appetite and preferences Increases variety of food choices Can be used to match insulin bolus doses to food intake

Carb Counting and Insulin Bolusing Insulin-to-Carb Ratio EXAMPLE: 1 unit insulin: 15 grams CHO Sample Meal 1 c. orange juice 30 g 2 slices toast 30 g ½ c. oatmeal 15 g 1 soft-cooked egg 1 tsp margarine Coffee & 1 T cream Total CHO: 75 g Insulin bolus: 5 units Sample Meal 2 slices wheat bread 30 g 2 oz. turkey breast Lettuce leaf, tomato slice 1 tsp mayonnaise 6-8 3-ring pretzels 15 g 2 small choc cookies 15 g Diet soda, 16 oz Total CHO: 60 g Insulin bolus: 4 units

Preventing Hypoglycemia Check BG 4-6 times per day Carry glucose tablets Have Glucagon Kit available

Hypoglycemia Treatment Guidelines The Rule of 15 If BG is 70 mg/dl or below Treat with 15 grams of carbohydrates (glucose tabs) Check BG in 15 minutes, and if not above 70 mg/dl, repeat treatment Glucagon Current emergency kit readily available and knowledgeable person trained to administer

Preventing Hyperglycemia and DKA Monitor BG 4-6 times per day Use Correction Boluses when appropriate Change infusion set every 2-3 days

Conclusions Insulin Pump Therapy is becoming widely recognized as the best way to treat insulin requiring diabetes Insulin pump is now considered standard of care in appropriate patients Pump Therapy has advantages over multi-dose therapy Insulin pumps can be continued in most patients who are admitted to the hospital

Basics of Continuous Subcutaneous Insulin Infusion Therapy. Lubna Mirza, MD Norman Endocrinology Associates 2018