Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Laboratório de Carboidratos e Radioimunoensaios (LIM-18), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
Diabetes Metab Res Rev. 2021 Jan;37(1):e3352. doi: 10.1002/dmrr.3352. Epub 2020 Jun 21.
11β-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 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; 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 × 1.73 m 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).
SNPs in the HSD11B1 gene may confer susceptibility to DKD and to IR in T1D individuals.
11β-羟类固醇脱氢酶 1（11β-Hydroxysteroid dehydrogenase 1，11β-HSD1）在代谢紊乱导致胰岛素抵抗（Insulin resistance，IR）中起作用，其编码基因（HSD11B1）的单核苷酸多态性（Single nucleotide polymorphisms，SNPs）与 2 型糖尿病和代谢综合征有关。在 1 型糖尿病（Type 1 diabetes，T1D）中，IR 与慢性并发症的发展有关。我们研究了巴西 T1D 个体中 HSD11B1 SNPs 与微血管并发症和 IR 的关系。
对 466 名 T1D 患者（57%为女性；中位年龄 37 岁，糖尿病病程 25 年，HbA1c 为 8.4%）的 5 个 SNPs 进行了基因分型。
rs11799643 的次要等位基因 T 与糖尿病视网膜病变（Diabetic retinopathy，DR）呈名义相关（OR=0.52；95%置信区间[CI]为 0.28-0.96；P=0.036）。rs17389016 的次要等位基因 C 与显性糖尿病肾病（Diabetic kidney disease，DKD）呈名义相关（OR=1.90；95%CI 为 1.07-3.37；P=0.028）。一项随访研究显示，29%的个体肾小球滤过率（Estimated glomerular filtration rate，eGFR）每年下降≥5 mL/min×1.73 m。在这些 eGFR 下降的个体（eGFR 下降者）中，rs17389016 的 C 等位基因比非下降者更常见（OR=2.10；95%CI 为 1.14-3.89；P=0.018）。最后，rs846906 的次要等位基因 T 与动脉高血压、更高的体重指数和腰围相关，从而导致胰岛素敏感性的替代标志物——葡萄糖处置率降低，这表明其存在风险（OR=1.23；95%CI 为 1.06-1.42；P=0.004）。
HSD11B1 基因中的 SNPs 可能使 T1D 个体易患 DKD 和 IR。
