Ping Li1, Kelly J Hunt, David J Taber, Rickey E Carter, Lindsey Kettinger, Deirdre Luttrell, Maria F Egidi, Nancy J Finch, Prabhakar Baliga, Angello Lin, Shari Biggins, Kathie L Hermayer. 1. 1 Medical University of South Carolina, Charleston, SC. 2 Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, People's Republic of China. 3 Mayo Clinic, Rochester, MN. 4 Azienda Ospedaliera Universitaria Pisana, Pisa, Italy. 5 Address correspondence to: Kathie L. Hermayer, M.D., M.S., F.A.C.E., Division of Endocrinology, Diabetes & Medical Genetics, Medical University of South Carolina, 96 Jonathan Lucas Street, Charleston, SC 29425.
Abstract
BACKGROUND: We previously reported that compared to standard glycemic control [blood glucose (BG): 70-180 mg/dL], patients randomized to intensive glycemic control (BG: 70-110 mg/dL) were at increased risk of graft rejection in renal transplantation. However, the underlying mechanisms that associate the effect of intensive glycemic control with renal transplant outcomes have not been identified. METHODS: A secondary data analysis of 93 participants (n=44 intensive, n=49 control) was conducted using data from a previous randomized controlled clinical trial. We examined inflammatory biomarkers, glycemic variability, hypoglycemia, and hyperglycemia as potential contributing etiologies by assessing the effect of intensive glycemic control on these characteristics, and evaluate the association of these variables with graft rejection. RESULTS: Intensive glycemic control had no appreciable effect on highly sensitive C-reactive protein, interleukin (IL)-6, tumor necrosis factor alpha, IL-1β, or IL-10 levels at all time points after transplantation. Moreover, neither inflammatory biomarkers nor increased glycemic variability were associated with graft rejection. However, intensive treatment increased the risk of hypoglycemia (BG <70 mg/dL, 84% vs. 25%, P<0.001). In sub-analysis, compared to non-rejecters, rejecters demonstrated higher rates of blood glucose below 70 mg/dL (90% vs. 49%, P=0.02). CONCLUSION: Inflammatory biomarkers and increased glycemic variability lack correlation with clinical outcomes in renal transplant, but importantly, increased perioperative hypoglycemic episodes (BG <70mg/dL) may be a salient etiology that contributed to the increased risk for acute allograft rejection related to intensive glycemic control. Further research is needed to confirm a causal association.
RCT Entities:
BACKGROUND: We previously reported that compared to standard glycemic control [blood glucose (BG): 70-180 mg/dL], patients randomized to intensive glycemic control (BG: 70-110 mg/dL) were at increased risk of graft rejection in renal transplantation. However, the underlying mechanisms that associate the effect of intensive glycemic control with renal transplant outcomes have not been identified. METHODS: A secondary data analysis of 93 participants (n=44 intensive, n=49 control) was conducted using data from a previous randomized controlled clinical trial. We examined inflammatory biomarkers, glycemic variability, hypoglycemia, and hyperglycemia as potential contributing etiologies by assessing the effect of intensive glycemic control on these characteristics, and evaluate the association of these variables with graft rejection. RESULTS: Intensive glycemic control had no appreciable effect on highly sensitive C-reactive protein, interleukin (IL)-6, tumor necrosis factor alpha, IL-1β, or IL-10 levels at all time points after transplantation. Moreover, neither inflammatory biomarkers nor increased glycemic variability were associated with graft rejection. However, intensive treatment increased the risk of hypoglycemia (BG <70 mg/dL, 84% vs. 25%, P<0.001). In sub-analysis, compared to non-rejecters, rejecters demonstrated higher rates of blood glucose below 70 mg/dL (90% vs. 49%, P=0.02). CONCLUSION: Inflammatory biomarkers and increased glycemic variability lack correlation with clinical outcomes in renal transplant, but importantly, increased perioperative hypoglycemic episodes (BG <70mg/dL) may be a salient etiology that contributed to the increased risk for acute allograft rejection related to intensive glycemic control. Further research is needed to confirm a causal association.
Authors: Clement Lo; Min Jun; Sunil V Badve; Helen Pilmore; Sarah L White; Carmel Hawley; Alan Cass; Vlado Perkovic; Sophia Zoungas Journal: Cochrane Database Syst Rev Date: 2017-02-27
Authors: Angela Sheu; Barbara Depczynski; Anthony J O'Sullivan; Grant Luxton; George Mangos Journal: J Diabetes Res Date: 2016-12-07 Impact factor: 4.011