大型 Bardet-Biedl 综合征临床人群的内分泌和代谢特征。

The Endocrine and Metabolic Characteristics of a Large Bardet-Biedl Syndrome Clinic Population.

机构信息

Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.

King's Diabetes Research Group, King's College London, London, United Kingdom.

出版信息

J Clin Endocrinol Metab. 2018 May 1;103(5):1834-1841. doi: 10.1210/jc.2017-01459.

DOI:10.1210/jc.2017-01459

PMID:29409041

Abstract

CONTEXT

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder in which previous reports have described obesity and a metabolic syndrome.

OBJECTIVE

We describe the endocrine and metabolic characteristics of a large BBS population compared with matched control subjects.

DESIGN

We performed a case-control study.

SETTING

This study was performed at a hospital clinic.

PATIENTS

Study patients had a clinical or genetic diagnosis of BBS.

MAIN OUTCOME MEASUREMENTS

Our study determined the prevalence of a metabolic syndrome in our cohort.

RESULTS

A total of 152 subjects were studied. Eighty-four (55.3%) were male. Mean (± standard deviation) age was 33.2 ± 1.0 years. Compared with age-, sex-, and body mass index-matched control subjects, fasting glucose and insulin levels were significantly higher in subjects with BBS (glucose: BBS, 5.2 ± 1.2 mmol/L vs control, 4.9 ± 0.9 mmol/L, P = 0.04; insulin: BBS, 24.2 ± 17.0 pmol/L vs control, 14.2 ± 14.8 pmol/L, P < 0.001). Serum triglycerides were significantly higher in subjects with BBS (2.0 ± 1.2 mmol/L) compared with control subjects (1.3 ± 0.8 mmol/L; P < 0.001), but total cholesterol, high-density lipoprotein, and low-density lipoprotein were similar in both groups. Systolic blood pressure was higher in the BBS group (BBS, 135 ± 18 mm Hg vs control subjects, 129 ± 16 mm Hg; P = 0.02). Alanine transaminase was raised in 34 (26.8%) subjects with BBS, compared with five (8.9%) control subjects (P = 0.01). The rate of metabolic syndrome, determined using International Diabetes Federation criteria, was significantly higher in the BBS group (54.3%) compared with control subjects (26% P < 0.001). Twenty-six (19.5%) of male subjects with BBS were hypogonadal (serum testosterone, 9.9 ± 5.3 mmol/L), but significant pituitary abnormalities were uncommon. Subclinical hypothyroidism was present in 24 of 125 (19.4%) patients with BBS, compared with 3 of 65 (4.6%) control subjects (P = 0.01).

CONCLUSIONS

Insulin resistance and the metabolic syndrome are increased in adult patients with BBS compared with matched control subjects. Increased subclinical hypothyroidism in the BBS cohort needs further investigation.

摘要

背景

Bardet-Biedl 综合征（BBS）是一种罕见的常染色体隐性遗传病，以往的报告描述了肥胖和代谢综合征。

目的

我们描述了与匹配的对照组相比，BBS 大人群的内分泌和代谢特征。

设计

我们进行了一项病例对照研究。

地点

这项研究在医院诊所进行。

患者

研究患者有 BBS 的临床或遗传诊断。

主要观察指标

我们的研究确定了我们队列中代谢综合征的患病率。

结果

共研究了 152 例患者。84 例（55.3%）为男性。平均（±标准差）年龄为 33.2 ± 1.0 岁。与年龄、性别和体重指数匹配的对照组相比，BBS 患者的空腹血糖和胰岛素水平显著升高（血糖：BBS，5.2 ± 1.2 mmol/L 与对照组，4.9 ± 0.9 mmol/L，P = 0.04；胰岛素：BBS，24.2 ± 17.0 pmol/L 与对照组，14.2 ± 14.8 pmol/L，P < 0.001）。BBS 组患者的血清三酰甘油明显高于对照组（2.0 ± 1.2 mmol/L 与 1.3 ± 0.8 mmol/L；P < 0.001），但两组总胆固醇、高密度脂蛋白和低密度脂蛋白相似。BBS 组的收缩压（BBS，135 ± 18 mm Hg 与对照组，129 ± 16 mm Hg；P = 0.02）较高。与对照组（8.9%）相比，34 例（26.8%）BBS 患者的丙氨酸转氨酶升高（P = 0.01）。使用国际糖尿病联合会标准，BBS 组的代谢综合征发生率（54.3%）明显高于对照组（26%，P < 0.001）。26 名（19.5%）男性 BBS 患者存在性腺功能减退（血清睾酮，9.9 ± 5.3 mmol/L），但明显的垂体异常并不常见。与 65 名对照组（4.6%）相比，125 名 BBS 患者中有 24 名（19.4%）存在亚临床甲状腺功能减退（P = 0.01）。