Heterogeneity of diabetes phenotype in patients with 3243 bp mutation of mitochondrial DNA (Maternally Inherited Diabetes and Deafness or MIDD)
Heterogeneity of diabetes phenotype in patients with 3243 bp mutation of mitochondrial DNA (Maternally Inherited Diabetes and Deafness or MIDD)
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DOI：
10.1016/s1262-3636(07)70105-2
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发表时间：
2004-04-01
影响因子：
7.2
通讯作者：
Timsit, J
中科院分区：
文献类型：
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作者：
Guillausseau, PJ;Dubois-Laforgue, D;Timsit, J
目的：在母系遗传性糖尿病伴耳聋（MIDD）患者中，由于线粒体DNA（mtDNA）3 243 A > G突变，糖尿病可能呈现出不同的表型。目的：确定一系列MIDD患者中是否存在两种不同的表型，MIDD1和MIDD2。设计：多中心前瞻性研究。患者：77名患有mtDNA 3243突变和139 名 1 型 (T1D) 或 2 型 (T2D) 糖尿病对照患者，根据糖尿病的初始表现、发病年龄、性别和糖尿病持续时间进行匹配（24 名 T1D 和 115 名 T2D，其中 55 名接受胰岛素治疗）。测量：人体测量特征（身高、体重、体重指数 [BMI]、性别）、糖尿病家族史和糖尿病特征（发病年龄、治疗、血红蛋白 A、 [HbA(1c)]），胰外表现。结果：13例（17%，MIDD1）糖尿病从发病起就表现为胰岛素依赖，其中6例伴有酮症酸中毒。 64例（83%，MIDD2）糖尿病类似T2D，12例采用饮食治疗，21例采用口服降糖药，31例采用胰岛素治疗。与 MIDD2 患者相比，MIDD1 患者首次出现 MIDD 症状的年龄较低（25.4 +/- 9.6 vs 33.7 +/- 13.2 岁，P < 0.0005），体重较低（49.1 +/- 7.4 vs 56.3 +/- 10.9 kg，P < 0.0025），BMI 较低（18.2 +/- 13.2 岁，P < 0.0005）。 2.3 vs 20.9 +/- 3.6 kg/m(2)，P < 0.0005)，以及更高的 HbA(1c) 水平（9.5 +/- 2.0 vs 7.5 +/- 1.6%，P < 0.0005）。两种 MIDD 亚型的糖尿病家族史和胰腺外表现的频率相同。当比较使用或不使用胰岛素治疗的患者时，没有发现 MIDD2 亚型存在差异。与匹配对照相比，MIDD患者的BMI较低（MIDD1/T1D 18.2 +/- 2.3 vs 24.0 +/- 3.6 kg/m(2)，MIDD2/T2D 20.9 +/- 3.6 vs 30.2 +/- 5.9 kg/m(2)，P < 0.0025）。最后，患有 MIDD 的男性患者身高比对照组短（MIDD1/T1D：166.1 +/- 3.2 vs 177.3 +/- 6.6 cm，MIDD2/T2D：168.4 +/- 7.2 vs 173.6 +/- 6.6 cm P < 0.025）。结论：这些结果证实了 MIDD 中存在两种不同的表型， MIDD1和MIDD2，可能与线粒体疾病的严重程度有关。其他遗传和/或环境因素在 MIDD 可变表型中的作用仍有待阐明。
Objective: In patients with maternally inherited diabetes and deafness (MIDD), due to 3 243 A > G mutation of mitochondrial DNA (mtDNA), diabetes may present with variable phenotypes.Objective: To ascertain the existence of two distinct phenotypes, MIDD1 and MIDD2, in a series of patients with MIDD.Design: Multicenter prospective study.Patients: 77 patients with diabetes and the mtDNA 3243 mutation and 139 control patients with type 1 (T1D) or type 2 (T2D) diabetes, matched according to initial presentation of diabetes, age at onset, sex, and duration of diabetes (24 T1D and 115 T2D, including 55 treated with insulin).Measurements: Anthropometric characteristics (height, body weight, body mass index [BMI], sex), family history of diabetes, and characteristics of diabetes (age at onset, treatment, hemoglobin A, [HbA(1c)]), extrapancreatic manifestations.Results: In 13 cases (17%, MIDD1), diabetes presented as insulin-dependent from the onset, with ketoacidosis in 6 cases. In 64 cases (83%, MIDD2), diabetes resembled T2D, and was treated with diet in 12 cases, oral hypoglycemic agents in 21 cases, or insulin in 31 cases. Compared with patients with MIDD2, patients with MIDD1 were characterized by lower age at onset of first manifestation of MIDD (25.4 +/- 9.6 vs 33.7 +/- 13.2 years, P < 0.0005), lower body weight (49.1 +/- 7.4 vs 56.3 +/- 10.9 kg, P < 0.0025), lower BMI (18.2 +/- 2.3 vs 20.9 +/- 3.6 kg/m(2), P < 0.0005), and higher HbA(1c) levels (9.5 +/- 2.0 vs 7.5 +/- 1.6%, P < 0.0005). Frequency of family history of diabetes and of extrapancreatic manifestations was the same in both MIDD subtypes. No difference was found within the MIDD2 subtype when comparing patients treated with or without insulin. Compared with matched controls, patients with MIDD had a lower BMI (MIDD1/T1D 18.2 +/- 2.3 vs 24.0 +/- 3.6 kg/m(2) and MIDD2/T2D 20.9 +/- 3.6 vs 30.2 +/- 5.9 kg/m(2), P < 0.0025). Lastly, male patients with MIDD had a shorter height than controls (MIDD1/T1D: 166.1 +/- 3.2 vs 177.3 +/- 6.6 cm and MIDD2/T2D: 168.4 +/- 7.2 vs 173.6 +/- 6.6 cm P < 0.025).Conclusions: These results confirm the existence of two different phenotypes in MIDD, MIDD1 and MIDD2, which may be related to the severity of the mitochondrial disease. The role of other genetic and/or environmental factors in the variable phenotype of MIDD remains to be elucidated.