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Prognostic performance of metabolic indexes in predicting onset of type 1 diabetes.

Xu P, Wu Y, Zhu Y, Dagne G, Johnson G, Cuthbertson D, Krischer JP, Sosenko JM, Skyler JS, Diabetes Prevention Trial-Type 1 (DPT-1) Study Gro - Diabetes Care (2010)

Bottom Line: The optimal cutoff value for 2-h glucose (114 mg/dl) maintained sensitivity and specificity values >0.60.The hazard ratio for those with 2-h glucose ≥ 114 mg/dl compared with those with 2-h glucose <114 mg/dl was 2.96 (1.67-5.22).The optimal cutoff value determined for 2-h glucose provides additional guidance for clinicians to identify subjects for potential prevention treatments before the onset of impaired glucose tolerance.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, College of Medicine, University of South Florida, Tampa, Florida, USA. xup@epi.usf.edu

ABSTRACT

Objective: In this investigation we evaluated nine metabolic indexes from intravenous glucose tolerance tests (IVGTTs) and oral glucose tolerance tests (OGTTs) in an effort to determine their prognostic performance in predicting the development of type 1 diabetes in those with moderate risk, as defined by familial relation to a type 1 diabetic individual, a positive test for islet cell antibodies and insulin autoantibody, but normal glucose tolerance.

Research design and methods: Subjects (n = 186) who had a projected risk of 25-50% for developing type 1 diabetes within 5 years were followed until clinical diabetes onset or the end of the study as part of the Diabetes Prevention Trial-Type 1. Prognostic performance of the metabolic indexes was determined using receiver operating characteristic (ROC) curve and survival analyses.

Results: Two-hour glucose from an OGTT most accurately predicted progression to disease compared with all other metabolic indicators with an area under the ROC curve of 0.67 (95% CI 0.59-0.76), closely followed by the ratio of first-phase insulin response (FPIR) to homeostasis model assessment of insulin resistance (HOMA-IR) with an area under the curve value of 0.66. The optimal cutoff value for 2-h glucose (114 mg/dl) maintained sensitivity and specificity values >0.60. The hazard ratio for those with 2-h glucose ≥ 114 mg/dl compared with those with 2-h glucose <114 mg/dl was 2.96 (1.67-5.22).

Conclusions: The ratio of FPIR to HOMA-IR from an IVGTT provided accuracy in predicting the development of type 1 diabetes similar to that of 2-h glucose from an OGTT, which, because of its lower cost, is preferred. The optimal cutoff value determined for 2-h glucose provides additional guidance for clinicians to identify subjects for potential prevention treatments before the onset of impaired glucose tolerance.

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ROC AUC for various metabolic indexes. ●, 2-h glucose–OGTT; ○, FPIR; ▵, FPIR-to–HOMA-IR ratio; □, HOMA-IR.
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Figure 1: ROC AUC for various metabolic indexes. ●, 2-h glucose–OGTT; ○, FPIR; ▵, FPIR-to–HOMA-IR ratio; □, HOMA-IR.

Mentions: The ROC AUCs of various metabolic indexes for the prediction of progression to type 1 diabetes are summarized in Table 2. Fasting glucose from both IVGTTs and OGTTs performed poorly and did not demonstrate prognostic ability with the same AUC value of 0.49 (95% CI 0.40–0.59). Analysis of IVGTT fasting insulin demonstrated some prognostic value with an AUC value of 0.59 (0.5 – 0.68) although the estimate had borderline significance. The AUC estimate of HOMA-IR and FPIR exceeded 0.5, although the lower confidence limit for both variables fell slightly below 0.5 at 0.49 and 0.48, respectively, rendering them nonsignificant predictors. However, when the ratio of FPIR to HOMA-IR was analyzed, it resulted in an AUC value of 0.66 (0.57–0.74), representing the best index among the indexes derived from IVGTTs. The only statistically significant AUC among the standard indexes derived from OGTT testing was 2-h glucose, which yielded the greatest AUC value at 0.67 (0.59–0.76) of all metabolic indexes examined (Fig. 1). A composite index that included AUC glucose and peak C-peptide was developed, using the proportional hazard model [index = 3.54 × 10–4 (AUC glucose) − 0.15 × (peak C-peptide)]. The ROC AUC result for the OGTT composite index was 0.71 (0.63–0.79). Although higher than the FPIR-to–HOMA-IR ratio and the 2-h glucose, the differences were not significant. The prediction performance of antibody titers was evaluated for comparison. AUCs for ICA titer and IAA titer were 0.69 (0.61–0.77) and 0.67(0.58–0.76), respectively. They did not provide better prediction than 2-h glucose or the FPIR-to–HOMA-IR ratio (P > 0.05) in this population.


Prognostic performance of metabolic indexes in predicting onset of type 1 diabetes.

Xu P, Wu Y, Zhu Y, Dagne G, Johnson G, Cuthbertson D, Krischer JP, Sosenko JM, Skyler JS, Diabetes Prevention Trial-Type 1 (DPT-1) Study Gro - Diabetes Care (2010)

ROC AUC for various metabolic indexes. ●, 2-h glucose–OGTT; ○, FPIR; ▵, FPIR-to–HOMA-IR ratio; □, HOMA-IR.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2992179&req=5

Figure 1: ROC AUC for various metabolic indexes. ●, 2-h glucose–OGTT; ○, FPIR; ▵, FPIR-to–HOMA-IR ratio; □, HOMA-IR.
Mentions: The ROC AUCs of various metabolic indexes for the prediction of progression to type 1 diabetes are summarized in Table 2. Fasting glucose from both IVGTTs and OGTTs performed poorly and did not demonstrate prognostic ability with the same AUC value of 0.49 (95% CI 0.40–0.59). Analysis of IVGTT fasting insulin demonstrated some prognostic value with an AUC value of 0.59 (0.5 – 0.68) although the estimate had borderline significance. The AUC estimate of HOMA-IR and FPIR exceeded 0.5, although the lower confidence limit for both variables fell slightly below 0.5 at 0.49 and 0.48, respectively, rendering them nonsignificant predictors. However, when the ratio of FPIR to HOMA-IR was analyzed, it resulted in an AUC value of 0.66 (0.57–0.74), representing the best index among the indexes derived from IVGTTs. The only statistically significant AUC among the standard indexes derived from OGTT testing was 2-h glucose, which yielded the greatest AUC value at 0.67 (0.59–0.76) of all metabolic indexes examined (Fig. 1). A composite index that included AUC glucose and peak C-peptide was developed, using the proportional hazard model [index = 3.54 × 10–4 (AUC glucose) − 0.15 × (peak C-peptide)]. The ROC AUC result for the OGTT composite index was 0.71 (0.63–0.79). Although higher than the FPIR-to–HOMA-IR ratio and the 2-h glucose, the differences were not significant. The prediction performance of antibody titers was evaluated for comparison. AUCs for ICA titer and IAA titer were 0.69 (0.61–0.77) and 0.67(0.58–0.76), respectively. They did not provide better prediction than 2-h glucose or the FPIR-to–HOMA-IR ratio (P > 0.05) in this population.

Bottom Line: The optimal cutoff value for 2-h glucose (114 mg/dl) maintained sensitivity and specificity values >0.60.The hazard ratio for those with 2-h glucose ≥ 114 mg/dl compared with those with 2-h glucose <114 mg/dl was 2.96 (1.67-5.22).The optimal cutoff value determined for 2-h glucose provides additional guidance for clinicians to identify subjects for potential prevention treatments before the onset of impaired glucose tolerance.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, College of Medicine, University of South Florida, Tampa, Florida, USA. xup@epi.usf.edu

ABSTRACT

Objective: In this investigation we evaluated nine metabolic indexes from intravenous glucose tolerance tests (IVGTTs) and oral glucose tolerance tests (OGTTs) in an effort to determine their prognostic performance in predicting the development of type 1 diabetes in those with moderate risk, as defined by familial relation to a type 1 diabetic individual, a positive test for islet cell antibodies and insulin autoantibody, but normal glucose tolerance.

Research design and methods: Subjects (n = 186) who had a projected risk of 25-50% for developing type 1 diabetes within 5 years were followed until clinical diabetes onset or the end of the study as part of the Diabetes Prevention Trial-Type 1. Prognostic performance of the metabolic indexes was determined using receiver operating characteristic (ROC) curve and survival analyses.

Results: Two-hour glucose from an OGTT most accurately predicted progression to disease compared with all other metabolic indicators with an area under the ROC curve of 0.67 (95% CI 0.59-0.76), closely followed by the ratio of first-phase insulin response (FPIR) to homeostasis model assessment of insulin resistance (HOMA-IR) with an area under the curve value of 0.66. The optimal cutoff value for 2-h glucose (114 mg/dl) maintained sensitivity and specificity values >0.60. The hazard ratio for those with 2-h glucose ≥ 114 mg/dl compared with those with 2-h glucose <114 mg/dl was 2.96 (1.67-5.22).

Conclusions: The ratio of FPIR to HOMA-IR from an IVGTT provided accuracy in predicting the development of type 1 diabetes similar to that of 2-h glucose from an OGTT, which, because of its lower cost, is preferred. The optimal cutoff value determined for 2-h glucose provides additional guidance for clinicians to identify subjects for potential prevention treatments before the onset of impaired glucose tolerance.

Show MeSH
Related in: MedlinePlus