diabetes: what’s new? what’s next? robert p. hoffman, m.d. grand rounds june 1, 2007
TRANSCRIPT
![Page 1: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/1.jpg)
Diabetes:What’s New?What’s Next?
Robert P. Hoffman, M.D.
Grand Rounds
June 1, 2007
![Page 2: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/2.jpg)
Introduction
Frederick Allen 1919 “The knowledge of diabetes is advancing rapidly enough that even the patient whose outlook seems darkest should take courage to remain alive in the hope of a treatment that can be called curative”
1921 Banting and Best at the University of Toronto discovered insulin
![Page 3: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/3.jpg)
DCCT
1993 1441 subjects (age 13-35) randomized to
intensive versus conventional therapy Intensive diabetes therapy markedly
reduces risk of long term complications in adults and adolescents
Increased risk of severe hypoglycemia Did not tell us how to achieve good
control
![Page 4: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/4.jpg)
What’s New?, What’s Next?
New insulins New modes of delivery New tecnology Curative treatments Prevention
![Page 5: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/5.jpg)
New Insulins
![Page 6: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/6.jpg)
Insulin Structure
Zn
![Page 7: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/7.jpg)
Short Acting Insulins
0 1 2 3 4 5Time Hours
Insu
lin
Glu
cose
Normal
Regular
Lispro AspartGlulysine
![Page 8: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/8.jpg)
Long Acting Insulins
0 4 8 12 16 20 24Time Hours
NPH/Lente
INS
UL
IN
Glargine
Levomir
![Page 9: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/9.jpg)
Glargine
Zn
pH =7.4
pH =4
![Page 10: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/10.jpg)
Levomir
FFA
FFA
FFA
![Page 11: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/11.jpg)
Intensive Insulin Regimens
Bf Lu Su Bt
Lispro Lispro Lispro
GlargineLevomir
![Page 12: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/12.jpg)
Insulin Adjustment
Morn Lunch Supper Bed
LP LP GlaLP
![Page 13: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/13.jpg)
Intensive Insulin Regimens
Lispro Lispro Lispro NPH
BF Lu Su Bt
![Page 14: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/14.jpg)
Intensive Insulin Regimens
Lispro Lispro NPH
BF Lu Su Bt
NPH
![Page 15: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/15.jpg)
Intensive Insulin Adjustment
Morn Lunch Supper Bed
LP NLP N
![Page 16: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/16.jpg)
Advantages of New Insulins
Better post prandial glucose control Less nocturnal hypoglycemia Better schedule flexibility No major differences in overall glucose
control
![Page 17: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/17.jpg)
Inhaled Insulin
![Page 18: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/18.jpg)
Inhaled Insulin
Action profile similar to lispro Well tolerated by subjects Still need to take long acting Need to work out dosing
differences Small decrease in lung diffusion
capacity Long term safety unknown
![Page 19: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/19.jpg)
New Technology
![Page 20: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/20.jpg)
Continuous Glucose Monitoring
![Page 21: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/21.jpg)
Maia and Arau´jo; Diab Res Clin Pract 2007,
![Page 22: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/22.jpg)
![Page 23: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/23.jpg)
Wilson et al, Diabetes care 2007
![Page 24: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/24.jpg)
![Page 25: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/25.jpg)
Change from baseline at 1 and 3 months of AIC. Values are means SE. P values correspond to the difference in change from baseline between the continuous and control groups. F, continuous group (arm 1); f, biweekly group (arm 2); OE, control group. Deis et al Diabetes Care 2006
![Page 26: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/26.jpg)
Insulin Pumps
![Page 27: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/27.jpg)
Continuous Subcutaneous Insulin Infusion (CSII)
![Page 28: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/28.jpg)
Insulin Pumps
MiniMed
![Page 29: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/29.jpg)
Infusion Sets
![Page 30: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/30.jpg)
Results
![Page 31: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/31.jpg)
Adolescents and Pumps
White et al Diabetes 2000
![Page 32: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/32.jpg)
Randomized Adult
Tsui et al, Diabetes Care 2001
![Page 33: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/33.jpg)
Randomized school age adolescents
Garcia-Garcia J Ped Endo Metab 2007– At 24 months randomized study MDI versus CSII
– Hemoglobin A1c was 7.70 +/- 0.64% vs 7.54 +/- 0.74% (p = 0.8);
– Body mass index SDS was 0.33 +/- 0.74 vs 0.40 +/- 1.01 (p = 0.9);
– Total daily insulin requirements were 0.95 +/- 0.10 vs 1.05 +/- 0.18 U/kg (p = 0.4),
– Incidence of severe hypoglycemia was 0.00 +/- 0.00 vs 0.04 +/- 0.14 episodes/patient/year (p = 0.8); and
– Incidence of ketoacidosis was 0.20 +/- 0.27 vs 0.04 +/- 0.14 episodes/patient/year (p = 0.2).
![Page 34: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/34.jpg)
Preschool Children
Fox et al Diabetes Care 2007Wilson et al Diabetes Care 2005
![Page 35: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/35.jpg)
Hypoglycemia
![Page 36: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/36.jpg)
DKA-Metaanalysis
Eggar Diabetic Medicine 1997
![Page 37: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/37.jpg)
Advantages to CSII
Effectively treats “dawn” phenomenon– Adjust basal rate at 3 AM
No shots Bolus for snacks without extra shot Flexibility of meals, exercise and travel
– Decreased need for snacks
![Page 38: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/38.jpg)
Disadvantages to SCII
Requires more time/effort Contact sports, swimming, bathing can
be difficult Increased risk of DKA
![Page 39: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/39.jpg)
Cure
![Page 40: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/40.jpg)
Pancreas Transplant
Successful– 95% one year survival
– 70% one year insulin free
Problems– Life long immunosuppression
– Donor availability
Indications– Renal failure or near renal failure
– Combined pancreas kidney
![Page 41: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/41.jpg)
Islet Transplantation
![Page 42: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/42.jpg)
Results
Insulin free for 4 to 12 months– Normal hemoglobin A1c
– Near normal glucose profiles
– No complications
Problems– 2 cadaver pancreases per patient
– Harvesting technique critical
– Required immunosuppression
![Page 43: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/43.jpg)
Autologous Bone Marrow Transplant
![Page 44: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/44.jpg)
Complications
![Page 45: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/45.jpg)
Prevention
Diabetes Prevention Trial Type 1– First degree relatives type 1 diabetic patients
» High Risk-received subcutaneous insulin No effect
» Intermediate Risk-oral insulin ongoing enrollment
No effect
European Nicotinamide Diabetes Intervention Trial
– No effect
![Page 46: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/46.jpg)
TrialNet
Series of multicenter studies to prolong beta cell function or prevent type 1 diabetes
Prolong beta cell function– Anti CD3
– Anti CD20
– Anti CD3 plus GLP-1 agonist
Oral insulin
![Page 47: Diabetes: What’s New? What’s Next? Robert P. Hoffman, M.D. Grand Rounds June 1, 2007](https://reader035.vdocuments.net/reader035/viewer/2022081519/56649ecd5503460f94bda0ab/html5/thumbnails/47.jpg)
Conclusion
The knowledge of diabetes is advancing rapidly enough that all patients should work to maintain the best possible glycemic control to prevent complications now and in the future with the hope of new technologies and treatments that will make their task and lifestyle easier if not eliminate the disease all together.