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苏丹青少年起病 1 型糖尿病的临床特征、生物化学和 HLA-DRB1 状态。

Clinical features, biochemistry, and HLA-DRB1 status in youth-onset type 1 diabetes in Sudan.

机构信息

Sudanese Children's Diabetes Association, Khartoum, Sudan.

Life for a Child Program, Diabetes NSW, Glebe, New South Wales, Australia.

出版信息

Pediatr Diabetes. 2021 Aug;22(5):749-757. doi: 10.1111/pedi.13209. Epub 2021 Apr 20.

Abstract

OBJECTIVE

To further understand clinical and biochemical features, and HLA-DRB1 genotypes, in new cases of diabetes in Sudanese children and adolescents.

RESEARCH DESIGN AND METHODS

Demographic characteristics, clinical information, and biochemical parameters (blood glucose, HbA1c, C-peptide, autoantibodies against glutamic acid decarboxylase 65 [GADA] and insulinoma-associated protein-2 [IA-2A], and HLA-DRB1) were assessed in 99 individuals <18 years, recently (<18 months) clinically diagnosed with T1D. HLA-DRB1 genotypes for 56 of these Arab individuals with T1D were compared to a mixed control group of 198 healthy Arab (75%) and African (25%) individuals without T1D.

RESULTS

Mean ± SD age at diagnosis was 10.1 ± 4.3 years (range 0.7-17.6 years) with mode at 9-12 years. A female preponderance was observed. Fifty-two individuals (55.3%) presented in diabetic ketoacidosis (DKA). Mean ± SD serum fasting C-peptide values were 0.22 ± 0.25 nmol/L (0.66±0.74 ng/ml). 31.3% were autoantibody negative, 53.4% were GADA positive, 27.2% were IA-2A positive, with 12.1% positive for both autoantibodies. Association analysis compared to 198 controls of similar ethnic origin revealed strong locus association with HLA-DRB1 (p < 2.4 × 10 ). Five HLA-DRB1 alleles exhibited significant T1D association: three alleles (DRB103:01, DRB104:02, and DRB104:05) were positively associated, while three (DRB110:01, DRB115:02, and DRB115:03) were protective. DRB1*03:01 had the strongest association (odds ratio = 5.04, p = 1.7 × 10 ).

CONCLUSIONS

Young Sudanese individuals with T1D generally have similar characteristics to reported European-origin T1D populations. However, they have higher rates of DKA and slightly lower autoantibody rates than reported European-origin populations, and a particularly strong association with HLA-DRB1*03:01.

摘要

目的

进一步了解苏丹儿童和青少年新发糖尿病的临床和生化特征及 HLA-DRB1 基因型。

研究设计和方法

评估了 99 名年龄均<18 岁、近期(<18 个月)临床诊断为 1 型糖尿病的个体的人口统计学特征、临床信息和生化参数(血糖、HbA1c、C 肽、谷氨酸脱羧酶 65 [GADA]和胰岛素瘤相关蛋白 2 [IA-2A]自身抗体)。将其中 56 名阿拉伯个体的 HLA-DRB1 基因型与无 1 型糖尿病的 198 名健康阿拉伯(75%)和非洲(25%)个体的混合对照组进行比较。

结果

诊断时的平均年龄±标准差为 10.1±4.3 岁(范围 0.7-17.6 岁),模式为 9-12 岁。观察到女性优势。52 名个体(55.3%)表现为糖尿病酮症酸中毒(DKA)。平均±标准差血清空腹 C 肽值为 0.22±0.25nmol/L(0.66±0.74ng/ml)。31.3%为自身抗体阴性,53.4%为 GADA 阳性,27.2%为 IA-2A 阳性,12.1%为两种自身抗体阳性。与具有相似种族来源的 198 名对照进行关联分析显示,HLA-DRB1 存在强基因座关联(p<2.4×10)。5 个 HLA-DRB1 等位基因与 1 型糖尿病显著相关:3 个等位基因(DRB103:01、DRB104:02 和 DRB104:05)呈阳性关联,而 3 个(DRB110:01、DRB115:02 和 DRB115:03)呈保护性。DRB1*03:01 具有最强的相关性(比值比=5.04,p=1.7×10)。

结论

苏丹年轻的 1 型糖尿病患者一般具有与报道的欧洲起源 1 型糖尿病人群相似的特征。然而,与报道的欧洲起源人群相比,他们的 DKA 发生率较高,自身抗体发生率略低,并且与 HLA-DRB1*03:01 呈特别强的关联。

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