diabetes: what’s new? what’s next? robert p. hoffman, m.d. grand rounds june 1, 2007
TRANSCRIPT
Diabetes:What’s New?What’s Next?
Robert P. Hoffman, M.D.
Grand Rounds
June 1, 2007
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
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
What’s New?, What’s Next?
New insulins New modes of delivery New tecnology Curative treatments Prevention
New Insulins
Insulin Structure
Zn
Short Acting Insulins
0 1 2 3 4 5Time Hours
Insu
lin
Glu
cose
Normal
Regular
Lispro AspartGlulysine
Long Acting Insulins
0 4 8 12 16 20 24Time Hours
NPH/Lente
INS
UL
IN
Glargine
Levomir
Glargine
Zn
pH =7.4
pH =4
Levomir
FFA
FFA
FFA
Intensive Insulin Regimens
Bf Lu Su Bt
Lispro Lispro Lispro
GlargineLevomir
Insulin Adjustment
Morn Lunch Supper Bed
LP LP GlaLP
Intensive Insulin Regimens
Lispro Lispro Lispro NPH
BF Lu Su Bt
Intensive Insulin Regimens
Lispro Lispro NPH
BF Lu Su Bt
NPH
Intensive Insulin Adjustment
Morn Lunch Supper Bed
LP NLP N
Advantages of New Insulins
Better post prandial glucose control Less nocturnal hypoglycemia Better schedule flexibility No major differences in overall glucose
control
Inhaled Insulin
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
New Technology
Continuous Glucose Monitoring
Maia and Arau´jo; Diab Res Clin Pract 2007,
Wilson et al, Diabetes care 2007
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
Insulin Pumps
Continuous Subcutaneous Insulin Infusion (CSII)
Insulin Pumps
MiniMed
Infusion Sets
Results
Adolescents and Pumps
White et al Diabetes 2000
Randomized Adult
Tsui et al, Diabetes Care 2001
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).
Preschool Children
Fox et al Diabetes Care 2007Wilson et al Diabetes Care 2005
Hypoglycemia
DKA-Metaanalysis
Eggar Diabetic Medicine 1997
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
Disadvantages to SCII
Requires more time/effort Contact sports, swimming, bathing can
be difficult Increased risk of DKA
Cure
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
Islet Transplantation
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
Autologous Bone Marrow Transplant
Complications
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
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
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.