TY - JOUR
T1 - The Role of Genetic Variant rs13266634 in SLC30A8/ZnT8 in Postoperative Hyperglycemia after Major Abdominal Surgery
AU - Brunke-Reese, Deborah
AU - Ssentongo, Paddy
AU - Ssentongo, Anna E.
AU - Phillips, Brett E.
AU - Pauli, Eric M.
AU - Berg, Arthur
AU - Kelleher, Shannon L.
AU - Soybel, David I.
N1 - Funding Information:
Financial Support: This work was supported by the David L. Nahrwold Endowment and the Academic Enrichment Fund of the Department of Surgery, Penn State Hershey College of Medicine.
Publisher Copyright:
© 2019 Endocrine Society.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Context: Following major surgery, postoperative hyperglycemia (POHG) is associated with suboptimal outcomes among patients with diabetes and nondiabetic patients. A specific genetic variant, rs13266634 (c.973C>T; p.ARG325TRP) in zinc transporter SLC30A8/ZnT8, is associated with protection against type 2 diabetes (T2D), suggesting it may be actionable for predicting and preventing POHG. Objective: To determine independent and mediated influences of a genetic variant on POHG in patients undergoing a model major operation, complex ventral hernia repair (cVHR). Patients and Design: For 110 patients (mean body mass index, 34.9 ± 5.8; T2D history, 28%) undergoing cVHR at a tertiary referral center (January 2012 to March 2017), multivariable regression was used to correlate the rs13266634 variant to preoperative clinical, laboratory, and imaging-based indices of liver steatosis and central abdominal adiposity to POHG. Causal mediation analysis (CMA) was used to determine direct and mediated contributions of SLC30A8/ZnT8 status to POHG. Results: Variant rs13266634 was present in 61 patients (55.4%). In univariate models, when compared with patients with homozygous wild-type genotype (C/C, n = 49), rs13266634 was associated with significantly lower risks of POHG (OR, 0.30; 95% CI, 0.14 to 0.67; P = 0.0038). Multivariable regression indicated that the association was independent (OR, 0.39; 95% CI, 0.15 to 0.97; P = 0.040). Additionally, CMA suggested that rs13266634 protects against POHG directly and indirectly through its influence on liver steatosis and central adiposity. Conclusions: In medically complex patients undergoing major operations, the rs13266634 variant protects against POHG and its associated outcomes, through independent and mediated contributions. In C/C patients undergoing major operations, SLC30A8/ZnT8 may prove useful to stratify the risk of POHG and potentially as a therapeutic target.
AB - Context: Following major surgery, postoperative hyperglycemia (POHG) is associated with suboptimal outcomes among patients with diabetes and nondiabetic patients. A specific genetic variant, rs13266634 (c.973C>T; p.ARG325TRP) in zinc transporter SLC30A8/ZnT8, is associated with protection against type 2 diabetes (T2D), suggesting it may be actionable for predicting and preventing POHG. Objective: To determine independent and mediated influences of a genetic variant on POHG in patients undergoing a model major operation, complex ventral hernia repair (cVHR). Patients and Design: For 110 patients (mean body mass index, 34.9 ± 5.8; T2D history, 28%) undergoing cVHR at a tertiary referral center (January 2012 to March 2017), multivariable regression was used to correlate the rs13266634 variant to preoperative clinical, laboratory, and imaging-based indices of liver steatosis and central abdominal adiposity to POHG. Causal mediation analysis (CMA) was used to determine direct and mediated contributions of SLC30A8/ZnT8 status to POHG. Results: Variant rs13266634 was present in 61 patients (55.4%). In univariate models, when compared with patients with homozygous wild-type genotype (C/C, n = 49), rs13266634 was associated with significantly lower risks of POHG (OR, 0.30; 95% CI, 0.14 to 0.67; P = 0.0038). Multivariable regression indicated that the association was independent (OR, 0.39; 95% CI, 0.15 to 0.97; P = 0.040). Additionally, CMA suggested that rs13266634 protects against POHG directly and indirectly through its influence on liver steatosis and central adiposity. Conclusions: In medically complex patients undergoing major operations, the rs13266634 variant protects against POHG and its associated outcomes, through independent and mediated contributions. In C/C patients undergoing major operations, SLC30A8/ZnT8 may prove useful to stratify the risk of POHG and potentially as a therapeutic target.
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U2 - 10.1210/jc.2018-02588
DO - 10.1210/jc.2018-02588
M3 - Article
C2 - 31220282
AN - SCOPUS:85085563288
SN - 0021-972X
VL - 104
SP - 3877
EP - 3892
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 9
ER -