Browsing by Author "Cobelli, Claudio"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Early Impairment of Insulin Sensitivity, β-Cell Responsiveness, and Insulin Clearance in Youth with Stage 1 Type 1 Diabetes
    (Oxford University Press, 2021) Galderisi, Alfonso; Moran, Antoinette; Evans-Molina, Carmella; Martino, Mariangela; Santoro, Nicola; Caprio, Sonia; Cobelli, Claudio; Pediatrics, School of Medicine
    Context: Clinical onset of type 1 diabetes (Stage 3 T1D) is preceded by a presymptomatic phase characterized by multiple islet autoantibodies with normal glucose tolerance (Stage 1 T1D). Objective: The aim was to explore the metabolic phenotypes of β-cell function and insulin sensitivity and clearance in normoglycemic youth with Stage 1 T1D and compare them with healthy nonrelated peers during a 3-hour oral glucose tolerance test (OGTT). Methods: Twenty-eight lean youth, 14 with ≥2 islet autoantibodies (cases) and 14 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 β-cell responsiveness (φtotal) and insulin sensitivity (SI), allowing assessment of β-cell function by the disposition index (DI=φtotal×SI). Fasting insulin clearance (CL0) was calculated as the ratio between the fasting insulin secretion rate (ISR) and plasma insulin levels (ISR0/I0), while postload clearance (CL180) was estimated by the ratio of AUC of ISR over the plasma insulin AUC for the 3-hour OGTT (ISRAUC/IAUC). Participants with impaired fasting glucose, impaired glucose tolerance, or any OGTT glucose concentration ≥200 mg/dL were excluded. Results: Cases (10.5 years [8, 15]) exhibited reduced DI (P < .001) due to a simultaneous reduction in both φtotal (P < 0.001) and SI (P = .008) compared with controls (11.5 years [10.4, 14.9]). CL0 and CL180 were lower in cases than in controls (P = .005 and P = .019). Conclusion: Presymptomatic Stage 1 T1D in youth is associated with reduced insulin sensitivity and lower β-cell responsiveness, and the presence of blunted insulin clearance.
  • Thumbnail Image
    Item
    β-Cell Function and Insulin Sensitivity in Youth With Early Type 1 Diabetes From a 2-Hour 7-Sample OGTT
    (The Endocrine Society, 2023) Galderisi, Alfonso; Evans-Molina, Carmella; Martino, Mariangela; Caprio, Sonia; Cobelli, Claudio; Moran, Antoinette; Pediatrics, School of Medicine
    Context: The oral minimal model is a widely accepted noninvasive tool to quantify both β-cell responsiveness and insulin sensitivity (SI) from glucose, C-peptide, and insulin concentrations during a 3-hour 9-point oral glucose tolerance test (OGTT). Objective: Here, we aimed to validate a 2-hour 7-point protocol against the 3-hour OGTT and to test how variation in early sampling frequency impacts estimates of β-cell responsiveness and SI. Methods: We conducted a secondary analysis on 15 lean youth with stage 1 type 1 diabetes (T1D; ≥ 2 islet autoantibodies with no dysglycemia) who underwent a 3-hour 9-point OGTT. The oral minimal model was used to quantitate β-cell responsiveness (φtotal) and insulin sensitivity (SI), allowing assessment of β-cell function by the disposition index (DI = φtotal × SI). Seven- and 5-point 2-hour OGTT protocols were tested against the 3-hour 9-point gold standard to determine agreement between estimates of φtotal and its dynamic and static components, SI, and DI across different sampling strategies. Results: The 2-hour estimates for the disposition index exhibited a strong correlation with 3-hour measures (r = 0.975; P < .001) with similar results for β-cell responsiveness and SI (r = 0.997 and r = 0.982; P < .001, respectively). The agreement of the 3 estimates between the 7-point 2-hour and 9-point 3-hour protocols fell within the 95% CI on the Bland-Altman grid with a median difference of 16.9% (-35.3 to 32.5), 0.2% (-0.6 to 1.3), and 14.9% (-1.4 to 28.3) for DI, φtotal, and SI. Conversely, the 5-point protocol did not provide reliable estimates of φ dynamic and static components. Conclusion: The 2-hour 7-point OGTT is reliable in individuals with stage 1 T1D for assessment of β-cell responsiveness, SI, and DI. Incorporation of these analyses into current 2-hour diabetes staging and monitoring OGTTs offers the potential to more accurately quantify risk of progression in the early stages of T1D.