Relationship between
Gilbert Syndrome and Rate of Nephropathy in Patients with Type 1 Diabetes.
Singer S1, Pilpel N1, Pinhas-Hamiel
O1,2,3
1Juvenile Diabetes Center Maccabi
Health Care Services, 2Pediatric Endocrinology and Diabetes Unit,
Safra Children's Hospital, Chaim Sheba Medical Center, Tel Hashomer, 3The
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Background: Gilbert syndrome (GS)
is an inherited disease caused by mutations in the UGT1A1 gene, which results
in decreased activity of UDP-glucuronosyltransferase 1A1. Its worldwide
prevalence is 3-7% in all ethnic groups and it is characterized by mild
unconjugated hyperbilirubinaemia. Bilirubin, a powerful endogenous antioxidant,
significantly attenuates endothelial dysfunction in preclinical experiments. In
adult diabetic patients with GS, a markedly lower prevalence of diabetic
nephropathy was documented, suggesting a beneficial effect of hyperbilirubinemia.
Objectives: To compare the prevalence of GS among individuals with type
1 diabetes mellitus (T1DM) to those without diabetes, and to compare the
prevalence of nephropathy in individuals with both T1DM and GS to those with T1DM
only.
Patients: The study group constituted 401 (204 female, 197
male) patients with T1DM, median age 21.0, (interquartile range, 15.7-27.9) with
median disease duration 10.8 years. (interquartile range, 5.7-15.8). Determination
of GS was based on the presence of unconjugated bilirubin ≥1.3 mg/dL. Prevalence
was compared to 98 obese children (control), median age 15.8, whose liver
function was studied. The prevalence of microalbuminuria was compared between
patients with diabetes and GS (group 1) and patients with diabetes alone (group
2) in a ratio of 1:2 matched by sex, age, and duration of diabetes.
Results: 43 patients (10.7%) with T1DM had GS compared to 3(3%) of the
control group. (p=0.016). There was no difference in the occurrence of GS
between males and females in subjects with T1DM 23(11.6%) males and 21 (10.3%)
females.
GS increased with age 6.9% among T1DM younger than
15 years compared to 11.8% of those older. The rate of nephropathy was 14.3% vs. 11.4%
for patients with T1DM and GS compared to those with T1DM alone.
Conclusions: The occurrence of GS was
almost 3 times higher among individuals with T1DM, and high compared to data in
the literature. The rate of nephropathy was similar among individuals with T1DM
and GS as to that of individuals with T1DM alone, suggesting no protective
value to elevated bilirubin in patients with T1DM.
