Inflammatory biomarkers, glycemic variability, hypoglycemia, and renal transplant outcomes: results of a randomized controlled trial.
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).


CONCLUSIONS
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.
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.
Ping
P
Li
Kelly J
KJ
Hunt
David J
DJ
Taber
Rickey E
RE
Carter
Lindsey
L
Kettinger
Deirdre
D
Luttrell
Maria F
MF
Egidi
Nancy J
NJ
Finch
Prabhakar
P
Baliga
Angello
A
Lin
Shari
S
Biggins
Kathie L
KL
Hermayer
D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000032:analysis*; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection; D006801:Humans; D006943:Hyperglycemia / Q000097:blood; D007003:Hypoglycemia / Q000097:blood; D007249:Inflammation / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000097:blood* / Q000601:surgery; D012307:Risk Factors; D016896:Treatment Outcome
D015415:Biomarkers; D001786:Blood Glucose; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016753:Interleukin-10; D002097:C-Reactive Protein