Type 2 diabetes mellitus phenotype and graft survival after islet transplantation.
BACKGROUND
Body fat accumulation decreases insulin sensitivity. It has being associated with earlier onset of type 1 diabetes mellitus (DM) and islet graft failure. The aim of this study was to evaluate whether insulin resistance, characterized by risk factors for type 2 DM, can predict islet graft survival in type 1 DM islet transplant (ITx) recipients.


METHODS
Demographic, anthropometrical, and laboratory data, as well as family history of type 2 DM (first degree relatives), were collected from 44 ITx recipients. Risk factors for type 2 DM, such as positive family history of type 2 DM (n=11) and overweight (body mass index >25 kg/m2; n=14), were analyzed separately and in combination, which was designated as "type 2 DM phenotype" (n=5). Differences in outcomes (time-to-graft dysfunction and failure) were compared using Kaplan-Meier curves. Cox regression analysis was performed to control for possible confounding factors.


RESULTS
Neither positive family history of type 2 DM nor overweight at baseline could predict islet function outcomes after ITx. However, when both risk factors were grouped, the "type 2 DM phenotype" was associated with earlier islet graft failure (mean estimate graft survival 25.7+/-9.1 vs. 54.1+/-5.2 months, P=0.022). These results were sustained after adjustments for confounding variables (OR 5.20, 95% CI 1.12-24.0).


CONCLUSIONS
Predisposition for type 2 DM can coexist with the type 1 DM phenotype and is associated with earlier decline in islet graft function. Prospective clinical trials should address whether it is associated with decreased insulin sensitivity and if insulin sensitizers play a role in prolonging islet graft survival.
Leitão
Cristiane B
CB
Diabetes Research Institute, Miami, FL, USA.
Bernetti
Karina
K
Tharavanij
Thipaporn
T
Cure
Pablo
P
Ricordi
Camillo
C
Alejandro
Rodolfo
R
D000328:Adult; D015992:Body Mass Index; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D006085:Graft Survival; D006801:Humans; D007333:Insulin Resistance; D016381:Islets of Langerhans Transplantation; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome