Patients with Gilbert syndrome and type 2 diabetes have lower prevalence of microvascular complications

OBJECTIVE: Accumulating clinical evidence indicates an inverse relationship between oxidative stress and unconjugated hyperbilirubinemia. This study aimed to compare the prevalence of diabetes microvascular complications in patients with Gilbert syndrome and type 2 diabetes mellitus (T2D). METHODS: A total of 1200 electronic records with T2D were reviewed. From them, 50 patients with Gilbert syndrome (cases [indirect bilirubin ≥1.2 mg/dl without evidence of hemolysis or liver disease]) and 50 controls (T2D without hyperbilirubinemia) were included. Linear and logistic regression models were performed to evaluate the independent association between indirect hyperbilirubinemia with microvascular complications related with T2D. RESULTS: Both case and control group had the same proportion of gender (female = 20 [40 %]) and diabetes duration (14.0 ± 6.5 years) and similar mean of age (60 ± 9.6 and 60 ± 9.2 years, respectively, p = 0.91). The median of unconjugated bilirubin of case and control group was 1.4 (1.2–1.6) vs. 0.4 (0.2–0.6) mg/dl (p < 0.001), respectively. Patients with elevated unconjugated bilirubin had less urine albumin-creatinine ratio compared with control group (8.5 [4.3–23] vs. 80 [8–408] mg/g, p < 0.001), and lower rate of diabetes microvascular complications and metabolic syndrome. After adjustment for BMI, age, HbA1c, blood pressure, triglycerides, and the metabolic syndrome, the lineal regression analysis showed that unconjugated bilirubin protects against microalbuminuria in T2D patients (β = −414.11, 95 % CI [-747.9, −80.3], p = 0.006. Also, unconjugated hyperbilirubinemia was independently associated with a better glomerular filtration rate (GFR) (β = 9.87, 95 % CI [1.5, 18.3], P = 0.02). CONCLUSIONS: Patients with Gilbert syndrome and T2D had a lower prevalence of diabetes microvascular complications.