The Role of Genetic Variant rs13266634 in SLC30A8/ZnT8 in Post-Operative Hyperglycemia after Major Abdominal Surgery Public

Context: Following major surgery, post-operative hyperglycemia (POHG) is associated with suboptimal outcomes and increased costs of care, among diabetics and non-diabetics. A specific genetic variant, rs13266634 in zinc transporter SLC30A8/ZnT8, is associated with protection against Type-2 Diabetes, suggesting it may be an actionable target for predicting and preventing POHG. Objective: To determine independent and mediated influences of a genetic variant, on post-operative hyperglycemia (POHG) in patients undergoing a model major operation, complex abdominal ventral hernia repair (cVHR). Patients and Methods: For 110 patients (mean BMI 34.95.8, T2D history 28%) undergoing cVHR at a tertiary referral center (January 2012 to March 2017), multivariate regression was used to correlate variant rs13266634 to pre-operative 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 to patients with rs13266634, the homozygous wild-genotype (WT/WT, n=59) was associated with significantly higher risks of POHG. Multivariate regression indicated that the association was independent. In addition, 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, rs13266634 protects against POHG and its associated outcomes, through independent and mediated contributions. In WT/WT patients undergoing major operations, SLC30A8/ZnT8 may prove useful to stratify risk of POHG and potentially as a therapeutic target.

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