A multi-year analysis of islet transplantation compared with intensive medical therapy on progression of complications in type 1 diabetes.
BACKGROUND
We hypothesized that transplantation of islets into type 1 diabetics could improve outcomes of glucose metabolism, renal function, retinopathy, and neuropathy compared with intensive medical therapy.


METHODS
We conducted a prospective, crossover, cohort study of intensive medical therapy (group 1) versus islet cell transplantation (group 2) in 42 patients. All were enrolled in group 1 then 31 crossed over with group 2 when islet donation became available. Transplantation was performed by portal venous embolization of more than 12,000 islet equivalents/kg body weight under cover of immunosuppression with antithymocyte globulin, tacrolimus, and mycophenolate. Outcome measures were HbA1c, change in glomerular filtration rate (GFR), progression of retinopathy, and change in nerve conduction velocity. This report details interim analysis of outcomes after 34+/-18 months (group 1) and 38+/-18 months (group 2).


RESULTS
HbA1c (%) in group 1 was 7.5+/-0.9 versus 6.6+/-0.7 in group 2 (P<0.01). GFR (mL/min/month) declined in both groups (group 1 -0.45+/-0.7 vs. group 2 -0.12+/-0.7, P=0.1). Slope of the GFR decline in group 1 was significantly more than 0. Retinopathy progressed in 10 of 82 eyes in group 1 versus 0 of 51 in group 2 (P<0.01). Nerve conduction velocity (m/sec) remained stable in group 1 (47.8+/-5 to 47.1+/-5 m/sec) and group 2 (47.2+/-4.5 to 47.7+/-3.5).


CONCLUSIONS
Islet transplantation yields improved HbA1c and less progression of retinopathy compared with intensive medical therapy during 3 years follow-up.
Warnock
Garth L
GL
Departments of Surgery, Ophthalmology & Visual Sciences, and Medicine, Ike Barber Human Islet Transplantation Laboratory, University of British Columbia, Vancouver, BC, Canada. gwarnock@interchange.ubc.ca
Thompson
David M
DM
Meloche
R Mark
RM
Shapiro
R Jean
RJ
Ao
Ziliang
Z
Keown
Paul
P
Johnson
James D
JD
Verchere
C Bruce
CB
Partovi
Nilufar
N
Begg
Iain S
IS
Fung
Michelle
M
Kozak
Sharon E
SE
Tong
Suet On
SO
Alghofaili
Khalid M
KM
Harris
Claire
C
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery*; D003928:Diabetic Nephropathies / Q000601:surgery*; D003929:Diabetic Neuropathies / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000503:physiopathology; D018450:Disease Progression; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D007677:Kidney Function Tests; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D055815:Young Adult
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin