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Variants inHSD11B1gene modulate susceptibility to diabetes kidney disease and to insulin resistance in type 1 diabetes

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Author(s):
Mori, Rosana Cristina ; Santos-Bezerra, Daniele Pereira ; Pelaes, Tatiana Souza ; Admoni, Sharon Nina ; Perez, Ricardo Vessoni ; Monteiro, Maria Beatriz ; Machado, Cleide Guimaraes ; Queiroz, Marcia Silva ; Machado, Ubiratan Fabres ; Correa-Giannella, Maria Lucia
Total Authors: 10
Document type: Journal article
Source: DIABETES-METABOLISM RESEARCH AND REVIEWS; v. 37, n. 1, p. 9-pg., 2020-06-21.
Abstract

Background and aim 11 beta-Hydroxysteroid dehydrogenase 1 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 ofHSD11B1SNPs with microvascular complications and with IR in a Brazilian cohort of T1D individuals. Materials and methods 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%). Results The minor allele T of rs11799643 was nominally associated with diabetic retinopathy (OR = 0.52; confidence interval [CI] 95% = 0.28-0.96;P= .036). The minor allele C of rs17389016 was nominally associated with overt diabetic kidney disease (DKD) (OR = 1.90; CI 95% = 1.07-3.37;P= .028). A follow-up study revealed that 29% of the individuals lost >= 5 mL min(-1)x 1.73 m(2)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; CI 95% = 1.14-3.89;P= .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; CI 95% = 1.06-1.42;P= .004). Conclusion SNPs in theHSD11B1gene may confer susceptibility to DKD and to IR in T1D individuals. (AU)

FAPESP's process: 16/15603-0 - Unraveling mechanisms of glycemic control and chronic complications of Diabetes mellitus: contributions to human health
Grantee:Ubiratan Fabres Machado
Support Opportunities: Research Projects - Thematic Grants