Shaat N, Ekelund M, Lernmark A, Ivarsson S, Nilsson A, Perfekt R, Berntorp K, Groop L
Department of Endocrinology, Lund University, Wallenberg Laboratory, University Hospital MAS, Malmo, Sweden.
Diabetologia. 2004 May;47(5):878-84. doi: 10.1007/s00125-004-1388-5. Epub 2004 Apr 17.
AIMS/HYPOTHESIS: Gestational diabetes mellitus is a heterogeneous disorder characterised by impaired insulin secretion and action. Our aim was to study whether autoimmunity, variations in genes affecting insulin secretion and action, or both, contribute to the development of gestational diabetes and whether the pathogenesis of the disease differs between women with a Scandinavian or Arabian background.
We studied a total of 500 unrelated women with gestational diabetes (400 Scandinavian and 100 Arabian) and 550 unrelated pregnant non-diabetic control women (428 Scandinavian and 122 Arabian) matched for ethnicity.
Arabian women with gestational diabetes were 50% more insulin resistant for the same BMI compared with Scandinavian women with the disease (homeostasis model assessment [HOMA-IR]; 3.2+/-0.3 vs 2.2+/-0.2, p=0.02). Both Scandinavian (4.2% vs 0.9%, p=0.008) and Arabian (4.6% vs 0.0%, p=0.03) women with gestational diabetes had a higher frequency of GAD antibodies (GAD65Ab) than the matched controls. The frequency of HLA-DQB1 risk genotypes was slightly higher in Scandinavian women with gestational diabetes than in the Scandinavian controls (46.3% vs 38.8%, p=0.03) but no significant difference was found between the Arabian women with gestational diabetes and the Arabian controls (47% vs 51.6%, p=0.47). There were no significant differences in the frequency of the insulin gene variable number of tandem repeat ( INS VNTR) alleles and genotypes or the peroxisome proliferator-activated receptor-gamma 2 ( PPAR gamma 2-Pro12Ala) polymorphism between the women with gestational diabetes and the control women either in Arabian or in Scandinavian women.
CONCLUSIONS/INTERPRETATION: Gestational diabetes mellitus was associated with the presence of GAD65Ab in both study groups. Scandinavian women with gestational diabetes may share some genetic features with Type 1 diabetes. In addition, Arabian women with gestational diabetes are more insulin resistant than Scandinavian women with gestational diabetes and with the same BMI.
目的/假设：妊娠期糖尿病是一种异质性疾病，其特征为胰岛素分泌和作用受损。我们的目的是研究自身免疫、影响胰岛素分泌和作用的基因变异或两者是否促成妊娠期糖尿病的发生，以及该疾病的发病机制在具有斯堪的纳维亚或阿拉伯背景的女性中是否存在差异。
我们共研究了500名无亲缘关系的妊娠期糖尿病女性（400名斯堪的纳维亚女性和100名阿拉伯女性）以及550名无亲缘关系的非糖尿病孕妇对照（428名斯堪的纳维亚女性和122名阿拉伯女性），两组在种族上匹配。
与患有该疾病的斯堪的纳维亚女性相比，患有妊娠期糖尿病的阿拉伯女性在相同体重指数下胰岛素抵抗高50%（稳态模型评估[HOMA-IR]；3.2±0.3对2.2±0.2，p = 0.02）。患有妊娠期糖尿病的斯堪的纳维亚女性（4.2%对0.9%，p = 0.008）和阿拉伯女性（4.6%对0.0%，p = 0.03）的谷氨酸脱羧酶抗体（GAD65Ab）频率均高于匹配的对照组。患有妊娠期糖尿病的斯堪的纳维亚女性中HLA-DQB1风险基因型的频率略高于斯堪的纳维亚对照组（46.3%对38.8%，p = 0.03），但患有妊娠期糖尿病的阿拉伯女性与阿拉伯对照组之间未发现显著差异（47%对51.6%，p = 0.47）。在患有妊娠期糖尿病的女性与对照组女性之间，无论是阿拉伯女性还是斯堪的纳维亚女性，胰岛素基因可变串联重复序列（INS VNTR）等位基因和基因型的频率，或过氧化物酶体增殖物激活受体γ2（PPARγ2-Pro12Ala）多态性均无显著差异。
结论/解读：在两个研究组中，妊娠期糖尿病均与GAD65Ab的存在相关。患有妊娠期糖尿病的斯堪的纳维亚女性可能与1型糖尿病有一些共同的遗传特征。此外，患有妊娠期糖尿病的阿拉伯女性比患有相同疾病且体重指数相同的斯堪的纳维亚女性胰岛素抵抗更强。
