67-OR: Oral Minimal Model Testing Reveals Early Impairment of Insulin Sensitivity in Type 1 Diabetes Autoantibody Positive, Nonobese, Nondysglycemic

• Published in: Diabetes (New York, N.Y.) Vol. 70
• Main Authors: Galderisi, Alfonso, Moran, Antoinette, Evans-Molina, Carmella, Martino, Mariangea, Santoro, Nicola, Caprio, Sonia, Cobelli, Claudio
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01.06.2021
• Subjects: Autoantibodies; Autoimmunity; Beta cells; Chromium; Diabetes; Diabetes mellitus (insulin dependent); Glucose; Glucose tolerance; Immunological tolerance; Insulin; Phenotypes
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db21-67-OR

Background: Clinical onset of type 1 diabetes (Stage 3 T1D) is preceded by a pre-symptomatic phase characterized by multiple islet autoimmunity with normal glucose tolerance (Stage 1 T1D), followed by dysglycemia (Stage 2). The metabolic phenotypes of beta-cell function and insulin sensitivity were explored in normoglycemic youth with stage 1 T1D and compared to healthy non-related peers during a 3-h oral glucose tolerance test (OGTT). Methods: Participants were recruited from TrialNet (cases) and Yale University (controls). Twenty-eight lean youth with at least two islet autoantibody (cases) and 32 healthy controls underwent a 3-hour 9-point OGTT with measurement of glucose, C-peptide and insulin. The oral minimal model was used to quantitate beta-cell responsivity (Phitotal) and insulin sensitivity (SI), allowing assessment of beta-cell function by the disposition index, DI=Phitotal x SI. Subjects with impaired fasting glucose, impaired glucose tolerance or any OGTT glucose concentration >200mg/dL were excluded. Results: Cases (10.5y[8, 15]) exhibited reduced DI (p<0.001) due to a simultaneous reduction in both Phitotal (p<0.001) and SI (p=0.008) as compared to controls (11.5y[10.4, 14.9]). Conclusion: Pre-symptomatic stage 1 T1D is associated with both reduced insulin sensitivity and lower beta cell responsiveness in youth.