Role of insulin resistance in predicting progression to type 1 diabetes.
OBJECTIVE
The purpose of this study was to determine whether insulin resistance is a risk factor for the development of type 1 diabetes in autoantibody-positive first-degree relatives of diabetic family members.


METHODS
Subjects (n = 186) who had a projected 25-50% risk for diabetes and subjects (n = 170) who had a projected >50% risk for type 1 diabetes in 5 years were followed until clinical diabetes onset or the end of the study as part of the Diabetes Prevention Trial-Type 1. We assessed insulin secretion with the first-phase insulin response (FPIR) and insulin resistance with homeostasis model assessment of insulin resistance (HOMA-IR) from an intravenous glucose tolerance test. The median follow-up was 4.3 years for moderate-risk subjects and 3.7 years for high-risk subjects.


RESULTS
During the follow-up period, 53 subjects in the moderate-risk group and 70 subjects in the high-risk group developed type 1 diabetes. After adjustments for confounders using multivariate analysis, HOMA-IR and the FPIR-to-HOMA-IR ratio were significantly associated with type 1 diabetes in both risk groups. In the moderate-risk population, the hazard ratio (HR) of HOMA-IR was 2.70 (95% CI 1.45-5.06) and the HR of FPIR-to-HOMA-IR was 0.32 (95% CI 0.18-0.57). In the high-risk population, the HR of HOMA-IR was 1.83 (95% CI 1.19-2.82) and the HR of FPIR-to-HOMA-IR was 0.56 (95% CI 0.40-0.78).


CONCLUSIONS
There is clear evidence of the association between insulin resistance and progression to type 1 diabetes. The combination of FPIR and HOMA-IR could be used as a better metabolic indicator for type 1 diabetes risk for prediction and suggests possible intervention strategies for diabetes prevention.
Xu
Ping
P
Pediatrics Epidemiology Center, University of South Florida, Tampa, Florida 33612, USA.
Cuthbertson
David
D
Greenbaum
Carla
C
Palmer
Jerry P
JP
Krischer
Jeffrey P
JP
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D018450:Disease Progression; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors
D001323:Autoantibodies