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Impaired glucose-induced glucagon suppression characterizes posttransplantation diabetes
Reduced glucose-induced insulin secretion and attenuated glucagon suppression during a hyperglycemic clamp characterize posttransplantation diabetes, according to study findings published in Diabetes Care.
Researchers wrote that the pathophysiologic defects can be improved or normalized with glucagon-like peptide-1 infusion.
Thea A. S. Halden, a PhD student in the section of nephrology, department of transplant medicine at Oslo University Hospital in Norway, and colleagues evaluated renal transplant recipients with (n = 12) and without (n = 12) posttransplantation diabetes to determine whether hyperglucagonemia plays a role in posttransplantation diabetes and to evaluate the insulinotropic and glucagonostatic effects of GLP-1 during fasting and hyperglycemic conditions.
All participants underwent two separate experimental days with 3-hour IV infusions of GLP-1 and saline; after 1 hour of infusion, a 2-hour hyperglycemic clamp was established. Ten minutes before the end of the clamp, arginine 5 g was given as an IV bolus.
Both groups had similar fasting concentration of glucagon and insulin. During the hyperglycemic period, the posttransplantation diabetes group had lower glucose-induced glucagon suppression compared with controls (maximal suppression from baseline, 43% in posttransplantation group vs. 65% in controls; P < .001). The posttransplantation group had a lower acute insulin response to arginine compared with controls (P = .01). Both groups had significant increases in the first- and second-phase insulin secretion with GLP-1 during the hyperglycemic period.
“Our findings suggest that the pathophysiology of [posttransplantation diabetes], in addition to inadequate insulin secretion, involves impaired glucose-induced glucagon suppression in the hyperglycemic state and that exogenously delivered GLP-1 improves both deficiencies in renal transplant recipients with [posttransplantation diabetes],” the researchers wrote. – by Amber Cox
Disclosure: The researchers report no relevant financial disclosures.