First-phase insulin response (FPIR) to intravenous glucose tolerance test (IVGTT), insulin sensitivity and long-term follow-up in ?- transfusion-dependent thalassemia (TDT) normoglycemic patients with reduced insulin secretion to oral glucose tolerance t

Abstract

Summary. Objective: To study the function of the endocrine pancreas in transfusion-dependent ?-thalassemia (?-TDT) patients with normal oral glucose tolerance test (OGTT) and hypoinsulinemia. Patients and methods: Seven ?-TDT patients (mean age 22.4 ± 4.2 years) with normal glucose tolerance test (NGT) and poor insulin response (hypoinsulinemia) to OGTT, not associated with ?-cell autoimmunity, were referred for a second opinion to an Italian Centre, part of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A). In this pilot study, the first-phase insulin response (FPIR), expressed as the sum of 1 and 3 minutes insulin, of ?-TDT patients to intravenous glucose tolerance test (IVGTT), was tested. Moreover, the long-term natural history was followed prospectively using an annual OGTT, with the aim of detecting any abnormality of glucose metabolism. Results: The FPIR value was between the 1st and 3rd percentile in two patients and between the 3rd and 10th percentile in five. After 43 ± 26 months (range 11 - 80 months) of follow-up, 2 patients developed impaired glucose tolerance (IGT), 3 both IGT and impaired fasting glucose (IFG) and two overt diabetes mellitus (DM). Interestingly, the patients who developed DM had, at baseline the lowest value of insulinogenic index (IGI, 0.08 and 0.25), defined as the ratio of the increment of plasma insulin to plasma glucose during the first 30 minutes after OGTT. Moreover, a significant correlation was found between the IGI at baseline and at follow-up in the patients who developed IGT with or without IFG (R= 0.927; P: 0.023). A significant reduction of Matsuda insulin sensitivity index (ISIM) and Insulin Secretion-Sensitivity Index-2 (ISSI-2) was documented in the study cohort at diagnosis of IFG, IGT and DM. There was a significant inverse correlation between ISSI-2 and area under the curve of plasma glucose (AUC-PG). Conclusions: These data demonstrated, for the first time, a progressive deterioration in glucose homeostasis in ?-TDT subjects with NGT and hypoinsulinemia. Thus, we consider that variations of insulin sensitivity could possibly have an impact on glucose tolerance in adult patients with TDT. Further investigations should focus on factors that might positively influence insulin sensitivity, including nutrition, drugs and physical activity.

Keywords

• Transfusion-dependent β-thalassemia, hypoinsulinemia, iron overload, oral glucose tolerance test, intravenous glucose tolerance test, glucose tolerance abnormalities, insulin resistance, follow-up