title: Glucose intolerance in thalassemia major is related to insulin resistance and hepatic dysfunction.
abstract: Glucose intolerance is a common consequence of transfusion therapy in patients with thalassemia major (TM), but the relative contribution of pancreatic damage and insulin resistance to glucose intolerance is unclear. We have investigated oral (OGTT) and intravenous (IVGTT) glucose tolerance, insulin sensitivity, and fasting concentrations of insulin, proinsulin, and des 31,32 proinsulin in 12 patients with TM (seven hepatitis C virus [HCV] antibody-negative and five-positive), eight patients with hepatic cirrhosis, and nine healthy controls. Two-hour plasma glucose concentrations were marginally higher in anti-HCV-negative (median, 7.4 mmol/ L; range, 4.0 to 8.2) and significantly so in anti-HCV-positive thalassemics (median, 8.5 mmol/L; range, 6.4 to to 23.0) and cirrhotics (median, 8.0 mmol/L; range, 4.7 to 17.6) than in controls (median, 5.5 mmol/L; range, 3.0 to 6.3). Insulin sensitivity was also reduced in the three patient groups (P < .05). Insulin resistance was the main determinant of oral glucose intolerance in all patient groups (partial r2 = .49, P < .0001, n = 28). In turn, the main determinants of insulin insensitivity in TM patients were liver damage (albumin, r = .67, P = .02) and serum ferritin concentration (r = -.62, P = .03). There was no relationship of either 2-hour or incremental insulin concentrations with ferritin levels or with HCV status in TM subjects. Moreover, these patients showed no elevation of concentrations of proinsulin and des 31,32 proinsulin, markers of pancreatic beta-cell damage, in excess of those observed in cirrhotic patients. In conclusion, the glucose intolerance of TM, like that of cirrhosis, is associated with insulin resistance, not insulin deficiency, and may be a direct or indirect consequence of hepatic damage.
authors.affiliation: Department of Medicine, University College London Medical School, Whittington Hospital, UK.
authors.forename: S
authors.initials: S
authors.lastname: Pappas
authors.forename: S M
authors.initials: SM
authors.lastname: Donohue
authors.forename: A E
authors.initials: AE
authors.lastname: Denver
authors.forename: V
authors.initials: V
authors.lastname: Mohamed-Ali
authors.forename: S
authors.initials: S
authors.lastname: Goubet
authors.forename: J S
authors.initials: JS
authors.lastname: Yudkin
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D005293:Ferritins / Q000097:blood; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000503:physiopathology*; D008297:Male; D017086:beta-Thalassemia / Q000503:physiopathology*
chemical_list: D005293:Ferritins