11β-hydroxysteroid dehydrogenase 1 (11βHSD1) has been implicated in insulin resistance (IR) in the setting of metabolic disorders, and single nucleotide polymorphisms (SNPs) in its encoding gene (HSD11B1) have been associated with type 2 diabetes and metabolic syndrome. In type 1 diabetes (T1D), IR has been related to the development of chronic complications. We investigated the association of HSD11B1 SNPs with microvascular complications and with IR in a Brazilian cohort of T1D individuals.
Five SNPs were genotyped in 466 T1D individuals (57% women; median of 37 years old, diabetes duration of 25 years and HbA1c of 8.4%).
The minor allele T of rs11799643 was nominally associated with diabetic retinopathy (OR=0.52; CI95%=0.28-0.96; p=0.036). The minor allele C of rs17389016 was nominally associated with overt diabetes kidney disease (DKD) (OR=1.90; CI95%=1.07-3.37; p=0.028). A follow-up study revealed that 29% of the individuals lost ≥ 5 mL.min .1.73m per year of the estimated glomerular filtration rate (eGFR). In these individuals (eGFR decliners), C allele of rs17389016 was more frequent than in non-decliners (OR=2.10; CI95%= 1.14-3.89; p=0.018). Finally, minor allele T of rs846906 associated with higher prevalence of arterial hypertension, higher body mass index and waist circumference, thus conferring risk to a lower estimated glucose disposal rate, a surrogate marker of insulin sensitivity (OR=1.23; CI95% = 1.06-1.42; p=0.004).
SNPs in the HSD11B1 gene may confer susceptibility to DKD and to IR in T1D individuals. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.