New Insulins and Insulin Delivery Systems Bruce W. Bode, MD, FACE Atlanta Diabetes Associates Atlanta, Georgia
Goals of Intensive Diabetes Management Near-normal glycemia HbA1c less than 6.5 to 7.0% Avoid short-term crisis Hypoglycemia Hyperglycemia DKA Minimize long-term complications Improve QOL ADA: Clinical Practice Recommendations. 2001.
Relative Risk of Progression of Diabetic Complications by Mean HbA1C Based on DCCT Data RELATIVE RISK 15 13 11 9 7 5 3 1 6 7 8 9 10 11 12 Retinop Neph Neurop Microalb Skyler, Endo Met Cl N Am 1996 HbA 1c
HbA1c and Plasma Glucose 26,056 data points (A1c and 7-point glucose profiles) from the DCCT Mean plasma glucose = (A1c x 35.6) 77.3 Post-lunch, pre-dinner, post-dinner, and bedtime correlated better with A1c than fasting, post-breakfast, or pre-lunch Rohlfing et al, Diabetes Care 25 (2) Feb 2002
Emerging Concepts The Importance of Controlling Postprandial Glucose
ACE / AACE Targets for Glycemic Control HbA 1c < 6.5 % Fasting/preprandial glucose Postprandial glucose < 110 mg/dl < 140 mg/dl ACE / AACE Consensus Conference, Washington DC August 2001
Insulin The most powerful agent we have to control glucose
The discovery of insulin (Toronto 1921) Fred Banting (1891 1941) Charles H. Best (1899-1978) John J.R. McLeod (1876-1935) James B. Collip (1892-1965) Marjorie (?-?)
The Miracle of Insulin Patient J.L., December 15, 1922 February 15, 1923
Comparison of Human Insulins / Analogues Insulin Onset of Duration of preparations action Peak action Regular 30 60 min 2 4 h 6 10 h NPH/Lente 1 2 h 4 8 h 10 20 h Ultralente 2 4 h Unpredictable 16 20 h Lispro/aspart 5 15 min 1 2 h 4 6 h Glargine 1 2 h Flat ~24 h
Ideal Basal/Bolus Insulin Absorption Pattern Breakfast Lunch Dinner Plasma insulin 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Time 8:00
Rapid-acting Insulin Analogs: Medical Rationale Administration at mealtime Mimic physiological insulin profile Improved postprandial glycemic control Lower risk of late hypoglycemia 5/8/2002 13
Primary Structure of Lys(B28), Pro(B29)-Insulin Insulin Gly Glu Phe Tyr Thr Pro Lys Thr 23 24 25 26 27 28 29 30 Lispro Gly Glu Phe Tyr Thr Lys Pro Thr
Primary Structure of Asp(B28)-Insulin Insulin Gly Glu Phe Tyr Thr Pro Lys Thr 23 24 25 26 27 28 29 30 Aspart Gly Glu Phe Tyr Thr Asp Lys Thr
Dissociation & Absorption of NovoLog Insulin Aspart (NovoLog ) Regular Human Insulin Subcutaneous Tissue Peak Time = 40-50 min Peak Time = 80-120 min Capillary Membrane
Insulin Aspart: Mean Serum Insulin Profiles During Euglycemic Clamp in Healthy Volunteers Serum insulin (pmol/l) 800 700 600 500 400 300 200 100 Insulin aspart Regular insulin 0 0 2 4 6 8 10 0.2 U/kg SQ Time (h) Heinemann L, et al. Diabetes Care. 1998;21:1910.
Glucose Area Under the Curve Glucose (mg/dl) 130 120 110 100 90 80 70 60 None Regular Aspart -30 Fast 30 60 90 120 240 Time (min)
Insulin Aspart vs Human Regular: Glycemic Control Plasma glucose Serum insulin mmol/l 18 16 14 12 10 8 6 mu/l 100 80 60 40 20 mg/dl 300 250 200 150 Insulin Aspart Human Regular 0 06:00 12:00 18:00 24:00 06:00 Breakfast Lunch Dinner NPH Home PD, et al. Diabetes Care. 1998;21:1904-1909.
Postprandial Blood Glucose Increment (Mean over the 3 Meals at 6 Months) P<0.001 P<0.001 1.8 Increment (mmol/l) 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 NovoLog Regular human insulin Prandial increment is the increase in blood glucose from premeal to 90 minutes postmeal 0.0 European trial North American trial Raskin P, et al. Diabetes Care. 2000;23:583. Home PD, et al. Diabetic Medicine. 2000;17:762.
Decreased Inter-individual Variability in NovoLog Values for Tmax 500 Healthy Volunteers NovoLog Regular human insulin 400 T max (min) 300 200 Outliers 100 Median 0 Study 1 Study 2 Study 3 Study 4 Data from: Home, Eur J Clin Pharmacol 1999; 55:199-203, Heinemann, Diab Med 1996; 13:683-4, Mudaliar, Diabetes Care 1999; 22:1501-6, Heinemann, Diabetes Care 1998; 21(11):1910-14.
Frequency of Minor* Hypoglycemia Observed by Level of Glycemic Control HbA 1c (%) 8.2 8.1 8.0 7.9 7.8 7.7 7.6 Type 1 Diabetes Frequency of Events: 0 / year 0 10 / year 10 30 / year >30 / year * symptoms or blood glucose < 45 mg/dl 0 NovoLog Regular insulin Study 035/EU NovoLog Regular insulin Study 036/US Novo Nordisk (data on file, studies 035/EU, 036/US )
Reduced Reporting of Major Nocturnal Hypoglycemia 14 12 % Patients with Major Hypoglycemic Episodes p<0.005 NS NovoLog Regular human insulin 10 8 6 4 2 0 Night-time Day-time Novo Nordisk (data on file, studies 035/EU, 036/US)
Reduced Risk of Major Nocturnal Hypoglycemia Relative Risk NovoLog Compared to Regular Human Insulin (1.0 = equal) 0.7 NovoLog Human insulin (N of patients with events) 0.5 Home 8% (54/707) 11% (39/358) Study 035/EU Study 036/US Raskin 4% (24/596) 8% (23/286) Novo Nordisk (data on file, studies 035/EU, 036/US)
Rapid-acting Insulin Analogues Provide Ideal Prandial Insulin Profile Breakfast Lunch Dinner Plasma insulin Aspart Aspart Aspart or or or Lispro Lispro Lispro 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Time 8:00
Short-Acting Insulin Analogs Lispro and Aspart Plasma Insulin Profiles Plasma insulin (pmol/l) 400 350 300 250 200 150 100 50 0 0 30 60 Regular Lispro 90 120 150 180 210 240 Time (min) Plasma insulin (pmol/l) 500 450 400 350 300 250 200 150 100 50 0 0 50 100 Regular Aspart 150 200 250 300 Time (min) Meal SC injection Meal SC injection Heinemann, et al. Diabet Med. 1996;13:625 629; Mudaliar, et al. Diabetes Care. 1999;22:1501 1506.
Pharmacokinetic Comparison NovoLog vs Humalog 350 Free Insulin (pmol/l) 300 250 200 150 100 NovoLog Humalog 50 0 Hedman, Diabetes Care 2001; 24(6):1120-21 7 8 9 10 11 12 13 Time (hours)
Long-acting Soluble Insulin Analogs: Medical Rationale Mimic basal physiological insulin profile Improved glycemic control More reproducible insulin delivery May be used in insulin pens 5/8/2002 28
Limitations of NPH, Lente, and Ultralente Do not mimic basal insulin profile Variable absorption Pronounced peaks Less than 24-hour duration of action Cause unpredictable hypoglycemia Major factor limiting insulin adjustments More weight gain
Insulin Glargine A New Long-Acting Insulin Analog Modifications to human insulin chain Substitution of glycine at position A21 Addition of 2 arginines at position B30 Gradual release from injection site Peakless, long-lasting insulin profile Gly 1 5 10 15 20Asp Substitution 1 5 10 15 20 25 30 Extension Arg Arg
Glargine vs NPH Insulin in Type 1 Diabetes Action Profiles by Glucose Clamp Glucose utilization rate (mg/kg/h) 6 5 4 3 2 1 0 0 10 Time (h) after SC injection NPH Glargine 20 30 End of observation period Lepore, et al. Diabetes. 1999;48(suppl 1):A97.
Overall Summary: Glargine Insulin glargine has the following clinical benefits Once-daily dosing because of its prolonged duration of action and smooth, peakless timeaction profile Comparable or better glycemic control (FBG) Lower risk of nocturnal hypoglycemic events Safety profile similar to that of human insulin
Type 2 Diabetes A Progressive Disease Over time, most patients will need insulin to control glucose
Insulin Therapy in Type 2 Diabetes Indications Significant hyperglycemia at presentation Hyperglycemia on maximal doses of oral agents Decompensation Acute injury, stress, infection, myocardial ischemia Severe hyperglycemia with ketonemia and/or ketonuria Uncontrolled weight loss Use of diabetogenic medications (eg, corticosteroids) Surgery Pregnancy Renal or hepatic disease
6-16 Mimicking Nature The Basal/Bolus Insulin Concept
The Basal/Bolus Insulin Concept Basal insulin Suppresses glucose production between meals and overnight 40% to 50% of daily needs Bolus insulin (mealtime) Limits hyperglycemia after meals Immediate rise and sharp peak at 1 hour 10% to 20% of total daily insulin requirement at each meal
Basal vs Mealtime Hyperglycemia in Diabetes 250 Basal hyperglycemia Mealtime hyperglycemia Plasma Glucose (mg/dl) 200 150 100 50 Type 2 Diabetes Normal 0 0600 1200 1800 2400 Time of Day 0600 AUC from normal basal >1875 mgm/dl. hr; Est HbA1 c >8.7% Riddle. Diabetes Care. 1990;13:676-686. 6-18
6-18 Basal vs Mealtime Hyperglycemia in Diabetes When Basal Corrected 250 Basal hyperglycemia Mealtime hyperglycemia Plasma Glucose (mg/dl) 200 150 100 50 Normal 0 0600 1200 1800 2400 0600 Time of Day AUC from normal basal 900 mgm/dl. hr; Est HbA1 c 7.2%
6-18 Basal vs Mealtime Hyperglycemia in Diabetes When Mealtime Hyperglycemia Corrected 250 Basal hyperglycemia Mealtime hyperglycemia Plasma Glucose (mg/dl) 200 150 100 50 Normal 0 0600 1200 1800 2400 0600 Time of Day AUC from normal basal 1425 mgm/dl. hr; Est HbA1 c 7.9
6-18 Basal vs Mealtime Hyperglycemia in Diabetes When Both Basal & Mealtime Hyperglycemia Corrected 250 Basal hyperglycemia Mealtime hyperglycemia Plasma Glucose (mg/dl) 200 150 100 50 Normal 0 0600 1200 1800 2400 0600 Time of Day AUC from normal basal 225 mgm/dl. hr; Est HbA1 c 6.4%
6-19 MIMICKING NATURE WITH INSULIN THERAPY Over time, most patients will need both basal and mealtime insulin to control glucose
6-37 Starting With Basal Insulin Advantages 1 injection with no mixing Insulin pens for increased acceptance Slow, safe, and simple titration Low dosage Effective improvement in glycemic control Limited weight gain
Treatment to Target Study: NPH vs Glargine in DM2 patients on OHA Add 10 units Basal insulin at bedtime (NPH or Glargine) Continue current oral agents Titrate insulin weekly to fasting BG < 100 mg/dl - if 100-120 mg/dl, increase 2 units - if 120-140 mg/dl, increase 4 units - if 140-160 mg/dl, increase 6 units - if 160-180 mg/dl, increase 8 units
Treatment to Target Study; A1C Decrease 9 M ean H ba 1c% 8.5 8 7.5 7 8.6 7.5 7.1 6.9 6.5 0 5 10 15 20 W eeks in Study (N =401)
Patients in Target (A1c < 7%) P ercentage of P a tien ts 70 60 50 40 30 20 10 0 66.2 48.8 32.3 2.5 W eek 0 W eek 8 W eek 12 W eek 18
Advancing Basal/Bolus Insulin Indicated when FBG acceptable but HbA1c > 7% or > 6.5% and/or SMBG before dinner > 140 mg/dl Insulin options To glargine or NPH, add mealtime aspart / lispro To suppertime 70/30, add morning 70/30 Consider insulin pump therapy Oral agent options Usually stop sulfonylurea Continue metformin for weight control Continue glitazone for glycemic stability?
6-46 Starting With Bolus Insulin Combination Oral Agents + Mealtime Insulin
Starting With Bolus Insulin Mealtime Lispro vs NPH or Metformin Added to Sulfonylurea 6-47 HbA 1c (%) 12 10 8 6 4 2 0 10.0% 2.3% 3.4 kg Su + LP (n = 42) 10.4% 1.9% 2.3 kg Su + NPH (n = 50) 10.2% 1.9% 0.9 kg Su + Metformin (n = 40) 12 10 8 6 4 2 0 Weight Gain (kg) Baseline HbA 1c Follow-up HbA 1c Follow-up Weight Browdos, et al. Diabetes. 1999;48(suppl 1):A104.
Case #1: DM 2 on SU with infection 49 year old white male DM 2 onset age 43, wt 173 lbs, Ht 70 inches On glimepiride (Amaryl) 4 mg/day, HbA1c 7.3% (intolerant to metformin) Infection in colostomy pouch (ulcerative colitis) glucose up to 300 mg/dl plus SBGM 3 times per day
Case #1: DM 2 on SU with infection Started on MDI; starting dose 0.2 x wgt. in lbs. Wgt. 180 lbs which = 36 units Bolus dose (lispro/aspart) = 20% of starting dose at each meal, which = 7 to 8 units ac (tid) Basal dose (glargine) = 40% of starting dose at HS, which = 14 units at HS Correction bolus = (BG - 100)/ SF, where SF = 1500/total daily dose; SF = 40
Correction Bolus Formula Current BG - Ideal BG Glucose Correction factor Example: Current BG: 220 mg/dl Ideal BG: 100 mg/dl Glucose Correction Factor: 40 mg/dl 220-100 40 =3.0u
Case #1: DM 2 on SU with infection Started on MDI Did well, average BG 138 mg/dl at 1 month and 117 mg/dl at 2 months post episode with HbA1c 6.1%
Strategies to Improve Glycemic Control: Type 2 Diabetes Monitor glycemic targets Fasting and postprandial glucose, HbA 1c Self-monitoring of blood glucose is essential Nutrition and activity are cornerstones of therapy Combinations of pharmacologic agents are often necessary to achieve glycemic targets
Intensive Therapy for Type 1 Diabetes Careful balance of food, activity, and insulin Daily self-monitoring BG Patient trained to vary insulin and food Define target BG levels (individualized) Frequent contact of patient and diabetes team Monitoring HbA 1c Basal / Bolus insulin regimen
Options in Insulin Therapy Current Multiple injections Insulin pump (CSII) Future Implant (artificial pancreas) Transplant (pancreas; islet cells)
Physiological Serum Insulin Secretion Profile Plasma insulin ( (µu/ml) 75 50 25 Breakfast Lunch Dinner 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Time 8:00
Classical Split-mixed Treatment Program Breakfast Lunch Dinner Plasma insulin REG NPH/Lente REG NPH/Lente 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Time 8:00
Split-mixed Program with Bedtime Intermediate Insulin Breakfast Lunch Dinner Plasma insulin REG NPH/Lente REG NPH/Lente 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Time 8:00
Basal/Bolus Insulin Absorption Pattern Standard Insulin Preparations Breakfast Lunch Dinner Plasma insulin REG REG REG NPH/Lente 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Time 8:00
Basal/Bolus Treatment Program with Rapid-acting and Long-acting Analogs Breakfast Lunch Dinner Plasma insulin Aspart Aspart Aspart or or or Lispro Lispro Lispro Glargine or Detemir 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Time 8:00
Novo Nordisk devices in diabetes care First pen (NovoPen 1) launched in 1985 Committed to developing one new insulin administration system per year.
Lilly Insulin Pens
Introducing InDuo The world s first combined insulin doser and blood glucose monitoring system A major breakthrough in Diabetes Care
InDuo - Integration Feature Combined insulin doser and blood glucose monitor
InDuo - Compact Size Feature Compact, discreet design Benefit Allows discreet testing and injecting anywhere, anytime
InDuo - Doser Remembers Feature Remembers amount of insulin delivered and time since last dose Benefit Helps people inject the right amount of insulin at the right time
Variable Basal Rate: CSII Program Breakfast Lunch Dinner Plasma insulin Bolus Bolus Bolus Basal infusion 4:00 8:00 12:00 16:00 20:00 24:00 4:00 Time 8:00
Variability of Insulin Absorption CSII <2.8% Subcutaneous Injectable 10% to 52% Fraction at inj. site 1.00 0.75 0.50 0.25 Fast (n = 12) Semilente (n = 9) Intermediate (n = 36) Lauritzen. Diabetologia. 1983;24:326 329. 0 6 12 18 24 30 36 42 48 Hours after single SC injections Femoral region
History of Pumps
PARADIGM PUMP Paradigm. Simple. Easy.
Pump Infusion Sets Softset QR Silhouette
Metabolic Advantages with CSII Improved glycemic control Better pharmacokinetic delivery of insulin Less hypoglycemia Less insulin required Improved quality of life
CSII Reduces HbA 1c HbA 1c 10.0 9.5.09 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 Pre-pump Post-pump Bell Rudolph Chanteleau Bode Boland Chase n = 58 n = 107 n = 116 n = 50 n = 25 n = 56 Mean dur. = 36 Mean dur. = 36 Mean dur. = 54 Mean dur. = 42 Mean dur. = 12 Mean dur. = 12 Adults Adolescents Chantelau E, et al. Diabetologia. 1989;32:421 426; Bode BW, et al. Diabetes Care. 1996;19:324 327; Boland EA, et al. Diabetes Care. 1999;22:1779 1784; Bell DSH, et al. Endocrine Practice. 2000;6:357 360; Chase HP, et al. Pediatrics. 2001;107:351 356.
CSII Reduces Hypoglycemia Events per hundred patient years 160 140 120 100 80 60 40 20 0 n = 55 Mean age 42 Pre-pump n = 107 Mean age 36 Post-pump Bode Rudolph Chanteleau Boland Chase n = 116 Mean age 29 n = 25 Mean age 14 n = 56 Mean age 17 Chantelau E, et al. Diabetologia. 1989;32:421 426; Bode BW, et al. Diabetes Care. 1996;19:324 327; Boland EA, et al. Diabetes Care. 1999;22:1779 1784; Chase HP, et al. Pediatrics. 2001;107:351 356.
CSII Factors Affecting HbA 1c Monitoring HbA 1c = 8.3 - (0.21 x BG per day) Recording 7.4 vs 7.8 Diet practiced CHO: 7.2 Fixed: 7.5 Other: 8.0 Insulin type Lispro: 7.3 R: 7.7
Insulin aspart versus buffered R versus insulin lispro in CSII study: Insulin aspart Screening Buffered regular human insulin (Velosulin ) Insulin lispro 2 0 16 weeks weeks weeks! 146 patients in the USA; 2 25 years with Type 1 diabetes; 7% HbA 1c 9%; previously treated with CSII for 3 months ode et al: Diabetes Care, March 2002
Glycemic Control with CSII 8.0 7.8 Type 1 Diabetes NovoLog Human insulin Humalog HbA 1c (%) 7.6 7.4 7.2 7.0 0 Baseline Week 8 Week 12 Week 16 Bode, Diabetes 2001 ; 50(S2):A106
Self-Monitored Blood Glucose in CSII 220 NovoLog Buffered Regular Humalog Blood Glucose (mg/dl) 200 180 160 140 120 100 * Type 1 Diabetes * * 80 Before and 90 min. after breakfast Before and 90 min. after lunch Before and Bedtime 2 AM 90 min. after dinner Bode, Diabetes 2001 ; 50(S2):A106
Symptomatic or Confirmed Hypoglycaemia p < 0.05 p < 0.05 Episodes/month/patient 12 10 8 6 4 2 0 30% relative reduction insulin aspart human insulin insulin lispro ode et al: Diabetes Care, March 2002
Insulin aspart versus buffered R versus insulin lispro in CSII study: pump compatibility Patients with trouble-free use (%) 50 40 30 20 10 0 Insulin aspart Buffered human insulin Insulin lispro ata on file (study ANA 2024)
Case Study: 54 year old DM1 on CSII with Lipoatrophy and Insulin Antibodies DM 1 onset age 21, 1968 CSII 1998, A1C 7.8% Lipoatrophy with humalog 1999-2000 Changed to Velosulin BR with still lipoatrophy Control suboptimal A1C 7.8%
Case Study: 54 year old DM1 on CSII with Lipoatrophy and Insulin Antibodies 7-10-01 A1C 7.8% on 28.8 units per day SMBG Avg BG 140, SD 118 based on 2.9 tests/day Insulin antibodies positive 1:32 Changed to Novolog 1 to 1 transfer 10-16-01 A1C 6.5% on 20.8 units per day SMBG Avg 118, SD 73 based on 3.0 tests per day
DM 1 CSII Patient: Humalog to Novolog 700 600 Humalog Average = 140 SD = 118 Novolog Average = 118 SD = 73 500 400 300 200 100 0 5/9/2001 5/29/2001 6/18/2001 7/8/2001 7/28/2001 8/17/2001 9/6/2001 9/26/2001 10/16/2001 11/5/2001
Case Study: 54 year old DM1 on CSII with Lipoatrophy and Insulin Antibodies 2-5-02 A1C 6.3% on 20 units per day SMBG Avg BG 104, SD 74 based on 3.1 tests/day
CSII Usage in Type 2 Patients Atlanta Diabetes Experience 10.00 9.00 9.2 8.00 7.00 6.00 7.57 7.19 5.00 N = 11 Baseline 6 months 18 months P = 0.026 P = 0.040 Mean HbA 1c (%)
Glycemic Control in Type 2 DM: CSII vs MDI in 127 patients A1C 8.4 8.2 8.0 7.8 7.6 7.4 7.2 7.0 Baseline End of Study (24 wks) CSII MDI Raskin, Diabetes 2001; 50(S2):A106
DM 2 Study: CSII vs MDI Overall treatment satisfaction improved in the CSII group: 59% pre to 79% at 24 weeks 93% in the CSII group preferred the pump to their prior regiment (insulin +/- OHA) CSII group had less hyperglycemic episodes (3 subjects, 6 episodes vs. 11 subjects, 26 episodes in the MDI group)
Insulin Reduction Following CSII 60 50 40 30 20 10 48.1-28% -18% -16% -17% 39.3 * 40.1 * 39.8* 34.5 * 0 Baseline (MDI) 15 days 6 mos 18 mos 36 mos n = 389 n = 389 n = 298 n = 246 n = 187 * P <0.001
Normalization of Lifestyle Liberalization of diet timing & amount Increased control with exercise Able to work shifts & through lunch Less hassle with travel time zones Weight control Less anxiety in trying to keep on schedule
Current Continuation Rate Continuous Subcutaneous Insulin Infusion (CSII) Continued 97% N = 165 Average Duration = 3.6 years Average Discontinuation <1%/yr Bode BW, et al. Diabetes. 1998;47(suppl 1):392. Discontinued 3%
U.S. Pump Usage Total Patients Using Insulin Pumps 162,000 150,000 120,000 100,000 81,000 60,000 50,000 6,600 8,700 11,400 15,000 20,000 26,500 35,000 43,000 0 '90 '91 '92 '93 '94 '95 '96 '97 '98 '99 2000 2001
Pump Therapy Indications HbA 1c >7.0% Frequent hypoglycemia Dawn phenomenon Hectic lifestyle Shift work Type 2 Exercise Pediatrics Pregnancy Gastroparesis Marcus. Postgrad Med. 1995.
Poor Candidates for CSII Unwilling to comply with medical follow-up Unwilling to perform self blood glucose monitoring 4 times daily Unwilling to quantitate food intake
Pump Therapy Basal rate Continuous flow of insulin Takes the place of NPH or ultralente insulin Units 6 5 4 3 2 1 Basal rate Meal boluses Insulin needed pre-meal Pre-meal BG Carbohydrates in meal Activity level Correction bolus for high BG Meal bolus 12 am 12 pm 12 am Time of day
If HbA 1c is Not to Goal Must look at: SMBG frequency and recording Diet practiced Do they know what they are eating? Do they bolus for all food and snacks? Infusion site areas Are they in areas of lipohypertrophy? Other factors: Fear of low BG Overtreatment of low BG
Future of Diabetes Management
Improvements in Insulin & Delivery Insulin analogs and inhaled insulin External pumps Internal pumps Continuous glucose sensors Closed-loop systems
GLUCOSE MONITORING SYSTEMS - Telemetry Consumer Product Real time glucose readings Wireless communication from sensor to monitor High and low glucose alarms FDA panel pending
losed-loop control using an external insulin ump and a subcutaneous glucose sensor + subcutaneous glucose sensor Insulin infusion pump (currently MiniMed 508)
Shift ~ ` ESC F1 F2 F3 F4 F5 F6 F7 F8 F 9 F10 F11 F12 Insert Delete Scroll Print 1 2 3 4 5 6 7 8 9 0 _ + - = { } Tab Q W E R T Y U I O P [ ] \ A S D F G H J K L : 1 2 Alt Alt,. / Shift Closed-Loop Setup for Canine Studies ; " Enter ' Z X C V B N M < >?
24-h Closed-Loop Control (diabetic canine) GLUCOSE (mg/dl) 500 400 300 200 100 start control adjust control parameters meals YSI GLC Sensor 0 6 am noon 6 pm midnight 6 am noon Closed Loop Resonse (U/h) 12 10 8 6 4 2 (U/h) µu/ml 100 75 50 25 Insulin (µu/ml) 0 0 6 am noon 6 pm midnight 6 am noon Time (h)
Implantable Pump Average HbA 1c 7.1% Hypoglycemic events reduce to 4 episodes per 100 pt-years
MiniMed 2007 System Implantable Insulin Pump Placement
Long-Term Glucose Sensor
ONG TERM IMPLANTABLE SYSTEM Human Clinical Trial 350 300 250 Glucose (mg/dl) 200 150 100 50 0 26 Thu 27 Fri 28 Sat 29 Sun 30 Mon 31 Tue 1 Nov 2 Thu 3 Fri 4 Sat 5 Sun 6 Mon 7 Tue Source: Medical Research Group, Inc.
Combine Pump and Sensor Technology + LTSS => Long Term Sensor System ( Open Loop Control ) Using an RF Telemetry Link...
Medtronic MiniMed s Implantable Biomechanical Beta Cell
Today s Reality Open-Loop Glucose Control Sensor # - 6347
LONG TERM IMPLANTABLE SYSTEM Automatic Glucose Regulation in a Fully Pancreatectomized Canine Manual Control Automatic Control Begins Control Terminated Manual Control Glucose (mg/dl) 400 350 300 250 200 150 100 50 CLOSED LOOP CONTROL 16 Wed 17 Thu 18 Fri 19 Sat 20 Sun 21 Mon 22 Tue 23 Wed August 2000 Source: Medical Research Group, Inc.
Summary Insulin remains the most powerful agent we have to control diabetes When used appropriately in a basal/bolus format, near-normal glycemia can be achieved Newer insulins and insulin delivery devices along with glucose sensors will revolutionize our care of diabetes
Conclusion Intensive therapy is the best way to treat patients with diabetes
QUESTIONS For a copy or viewing of these slides, contact WWW.adaendo.com