In:
Diabetes Care, American Diabetes Association, Vol. 46, No. 5 ( 2023-05-01), p. 1098-1105
Abstract:
Metabolic zones were developed to characterize heterogeneity of individuals with islet autoantibodies. RESEARCH DESIGN AND METHODS Baseline 2-h oral glucose tolerance test data from 6,620 TrialNet Pathway to Prevention Study (TNPTP) autoantibody-positive participants (relatives of individuals with type 1 diabetes) were used to form 25 zones from five area under the curve glucose (AUCGLU) rows and five area under the curve C-peptide (AUCPEP) columns. Zone phenotypes were developed from demographic, metabolic, autoantibody, HLA, and risk data. RESULTS As AUCGLU increased, changes of glucose and C-peptide response curves (from mean glucose and mean C-peptide values at 30, 60, 90, and 120 min) were similar within the five AUCPEP columns. Among the zones, 5-year risk for type 1 diabetes was highly correlated with islet antigen 2 antibody prevalence (r = 0.96, P & lt; 0.001). Disease risk decreased markedly in the highest AUCGLU row as AUCPEP increased (0.88–0.41; P & lt; 0.001 from lowest AUCPEP column to highest AUCPEP column). AUCGLU correlated appreciably less with Index60 (an indicator of insulin secretion) in the highest AUCPEP column (r = 0.33) than in other columns (r ≥ 0.78). AUCGLU was positively related to “fasting glucose × fasting insulin” and to “fasting glucose × fasting C-peptide” (indicators of insulin resistance) before and after adjustments for Index60 (P & lt; 0.001). CONCLUSIONS Phenotypes of 25 zones formed from AUCGLU and AUCPEP were used to gain insights into type 1 diabetes heterogeneity. Zones were used to examine GCRC changes with increasing AUCGLU, associations between risk and autoantibody prevalence, the dependence of glucose as a predictor of risk according to C-peptide, and glucose heterogeneity from contributions of insulin secretion and insulin resistance.
Type of Medium:
Online Resource
ISSN:
0149-5992
,
1935-5548
Language:
English
Publisher:
American Diabetes Association
Publication Date:
2023
detail.hit.zdb_id:
1490520-6