OBJECTIVE Molecular defects of hepatocyte nuclear factor 1B (HNF1B) are associated with a multiorgan disease, including diabetes (maturity-onset diabetes of the young 5) and kidney abnormalities. The HNF1B syndrome is related to HNF1B mutations or to a 17q12 deletion spanning 15 genes, including HNF1B. Here, we described HNF1B-related diabetes and associated phenotypes and assessed genotype/phenotype correlations at diagnosis and in the long-term.

RESEARCH DESIGN AND METHODS This multicenter retrospective cohort study included 201 patients, aged 18 years or older at follow-up, with HNF1B mutations (n = 101) or deletion (n = 100).

RESULTS Diabetes was present in 159 patients. At diagnosis, clinical symptoms of diabetes were present in 67 of 144 patients and HNF1B renal disease in 64 of 102. Although responsiveness to sulfonylureas/repaglinide was observed in 29 of the 51 tested, 111 of 140 patients (79%) were treated with insulin at follow-up. Diabetic retinopathy and/or neuropathy were present in 46 of 114 patients. Renal cysts were present in 122 of 166 patients, chronic kidney disease stages 3–4 (CKD3–4) in 75 of 169 (44%), and end-stage renal disease (ESRD) in 36 of 169 (21%). Compared with the patients with mutations, those with HNF1B deletion less often had CKD3–4/ESRD at diagnosis (11 of 43 vs. 27 of 35, P < 10⁻⁴) and in the long term (40 of 78 vs. 71 of 91, P = 0.0003). They were leaner and more frequently treated with insulin.

CONCLUSIONS In patients with HNF1B syndrome, diabetes complications, cardiovascular risk factors, CKD3–4, and ESRD are highly prevalent. At diabetes diagnosis, the presence of morphological and/or functional kidney disease may help etiological diagnosis. Genotype/phenotype correlations may have implications for the care and the prognosis of these patients.

目的肝细胞核因子1B（HNF1B）的分子缺陷与多器官疾病有关，包括糖尿病（5岁以下的成熟期糖尿病）和肾脏异常。HNF1B综合征与HNF1B突变或跨越15个基因（包括HNF1B）的17q12缺失有关。在这里，我们描述了HNF1B相关的糖尿病和相关的表型，并评估了诊断和长期的基因型/表型相关性。

研究设计和方法这项多中心回顾性队列研究包括201例年龄在18岁或以上的随访患者，这些患者具有HNF1B突变（n = 101）或缺失（n = 100）。

结果159例患者中存在糖尿病。在诊断时，144例患者中有67例出现糖尿病的临床症状，102例中有64例存在HNF1B肾病。尽管在51例接受测试的患者中有29例观察到对磺酰脲/瑞格列奈的反应，但140例患者中有111例（79％）接受了胰岛素治疗在后续行动中。114名患者中有46名存在糖尿病性视网膜病变和/或神经病变。166例患者中有122例存在肾囊肿，169例中的75例（44％）中有3–4期慢性肾脏病（CKD3-4），169例中的36例中有终末期肾脏疾病（ESRD）。与突变患者相比，HNF1B缺失的患者在诊断时（CK 3-4的11对比35的27，P <10 ^-4）和长期（78的40 VS 71的71）更少见。 91，P = 0.0003）。他们更苗条，更经常用胰岛素治疗。

结论在HNF1B综合征患者中，糖尿病并发症，心血管危险因素，CKD3-4和ESRD普遍存在。在糖尿病诊断中，形态和/或功能性肾脏疾病的存在可能有助于病因诊断。基因型/表型的相关性可能对这些患者的护理和预后有影响。