Caroline K Kramer1, Bernard Zinman1, Haysook Choi1, Ravi Retnakaran1. 1. Leadership Sinai Centre for Diabetes (C.K.K., B.Z., H.C., R.R.), Mt Sinai Hospital, Toronto, ON M5T 3L9, Canada; Division of Endocrinology (C.K.K., B.Z., R.R.), University of Toronto, Toronto, ON M5G 2C4, Canada; and Lunenfeld-Tanenbaum Research Institute (B.Z., R.R.), Mt Sinai Hospital, Toronto, ON M5G 1X5, Canada.
Abstract
CONTEXT: Hyperglucagonemia is a characteristic feature of type 2 diabetes (T2DM) that has been postulated to be due to β-cell dysfunction and the resultant loss of insulin-mediated α-cell suppression. When administered in early T2DM, short-term intensive insulin therapy (IIT) can improve β-cell function, resulting in reduced glycemic variability. OBJECTIVE: To evaluate the impact of IIT on hyperglucagonemia and its associations with β-cell function and glycemic variability. Design/Setting/Participants/Intervention: Sixty-two patients with T2DM of mean 3.0 ± 2.1 years duration and glycated hemoglobin of 6.8 ± 0.7% underwent 4 weeks of IIT, consisting of basal detemir and premeal insulin aspart. MAIN OUTCOME MEASURES: Glucagon response was measured by area under the glucagon curve (AUCglucagon) on oral glucose tolerance test at baseline and 1 day post-IIT. β-Cell function before and after IIT was assessed by Insulin Secretion-Sensitivity Index-2 and ΔISR0-120/Δglucose0-120*Matsuda index (where ISR is the prehepatic insulin secretion rate determined by C-peptide deconvolution). Glucose variability was assessed in both the first and last weeks by the coefficient of variation of capillary glucose on daily six-point self-monitoring profiles. RESULTS: Both Insulin Secretion-Sensitivity Index-2 and ΔISR0-120/Δglucose0-120*Matsuda index demonstrated improvement in β-cell function after IIT (both P ≤ .02), accompanied by reduced glycemic variability (P = .05). There was a marked reduction in AUCglucagon after IIT, as compared to baseline (P < .001). However, the decrease in AUCglucagon was not associated with the change in either β-cell measure (both P ≥ .34) or glucose variability (P = .37). CONCLUSIONS: Short-term IIT can reduce post-challenge hyperglucagonemia in early T2DM, but this effect does not appear to be due to improved β-cell function.
CONTEXT: Hyperglucagonemia is a characteristic feature of type 2 diabetes (T2DM) that has been postulated to be due to β-cell dysfunction and the resultant loss of insulin-mediated α-cell suppression. When administered in early T2DM, short-term intensive insulin therapy (IIT) can improve β-cell function, resulting in reduced glycemic variability. OBJECTIVE: To evaluate the impact of IIT on hyperglucagonemia and its associations with β-cell function and glycemic variability. Design/Setting/Participants/Intervention: Sixty-two patients with T2DM of mean 3.0 ± 2.1 years duration and glycated hemoglobin of 6.8 ± 0.7% underwent 4 weeks of IIT, consisting of basal detemir and premeal insulin aspart. MAIN OUTCOME MEASURES: Glucagon response was measured by area under the glucagon curve (AUCglucagon) on oral glucose tolerance test at baseline and 1 day post-IIT. β-Cell function before and after IIT was assessed by Insulin Secretion-Sensitivity Index-2 and ΔISR0-120/Δglucose0-120*Matsuda index (where ISR is the prehepatic insulin secretion rate determined by C-peptide deconvolution). Glucose variability was assessed in both the first and last weeks by the coefficient of variation of capillary glucose on daily six-point self-monitoring profiles. RESULTS: Both Insulin Secretion-Sensitivity Index-2 and ΔISR0-120/Δglucose0-120*Matsuda index demonstrated improvement in β-cell function after IIT (both P ≤ .02), accompanied by reduced glycemic variability (P = .05). There was a marked reduction in AUCglucagon after IIT, as compared to baseline (P < .001). However, the decrease in AUCglucagon was not associated with the change in either β-cell measure (both P ≥ .34) or glucose variability (P = .37). CONCLUSIONS: Short-term IIT can reduce post-challenge hyperglucagonemia in early T2DM, but this effect does not appear to be due to improved β-cell function.