Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial.
Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial.
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DOI：
10.1038/gim.2017.150
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Pollin TI
中科院分区：
文献类型：
--
作者：
Kleinberger JW;Copeland KC;Gandica RG;Haymond MW;Levitsky LL;Linder B;Shuldiner AR;Tollefsen S;White NH;Pollin TI
单基因糖尿病占糖尿病病例的1-2%。它往往未被诊断，这可能导致不适当的治疗。本研究旨在评估诊断为2型糖尿病（T2 D）的超重/肥胖青少年队列中单基因糖尿病的患病率。在TODAY临床试验中，对488名超重/肥胖T2 D青少年的种族/种族多样化队列进行了使用自定义单基因糖尿病基因组的测序。分析了单基因糖尿病变异与临床特征和治疗失败时间之间的关系。超过4%（22/488）的患者存在导致单基因糖尿病的遗传变异（7例GCK，7例HNF 4A，5例HNF 1A，2例INS和1例KLF 11）。单基因糖尿病患者的BMI Z评分、空腹胰岛素和空腹血糖均显著降低，但无临床意义。在研究组中，大多数（6/7）HNF 4A变体患者在TODAY治疗中迅速失败（HR=5.03，p=0.0002），而GCK变体患者均未治疗失败。在超重/肥胖的T2 D儿童和青少年队列中发现4.5%的单基因糖尿病患者，这表明在没有糖尿病相关自身抗体和维持C肽的儿童和青少年中应考虑单基因糖尿病诊断，无论BMI如何，因为它可能指导适当的临床管理。
Monogenic diabetes accounts for 1–2% of diabetes cases. It is often undiagnosed, which may lead to inappropriate treatment. This study was performed to estimate the prevalence of monogenic diabetes in a cohort of overweight/obese adolescents diagnosed with type 2 diabetes (T2D). Sequencing using a custom monogenic diabetes gene panel was performed on a racially/ethnically diverse cohort of 488 overweight/obese adolescents with T2D in the TODAY clinical trial. Associations between having a monogenic diabetes variant and clinical characteristics and time to treatment failure were analyzed. Over four percent (22/488) had genetic variants causing monogenic diabetes (7 GCK, 7 HNF4A, 5 HNF1A, 2 INS, and 1 KLF11). Patients with monogenic diabetes had a statistically, but not clinically, significant lower BMI Z-score, lower fasting insulin, and higher fasting glucose. Most (6/7) patients with HNF4A variants rapidly failed TODAY treatment across study arms (HR=5.03, p=0.0002), while none with GCK variants failed treatment. Discovery of 4.5% of patients with monogenic diabetes in an overweight/obese cohort of children and adolescents with T2D suggests monogenic diabetes diagnosis should be considered in children and adolescents without diabetes-associated autoantibodies and maintained C-peptide, regardless of BMI, as it may direct appropriate clinical management.
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DOI：
10.1097/00001648-199001000-00010
发表时间：
1990-01-01
期刊：
Epidemiology (Cambridge, Mass.)
影响因子：
--
作者：
Rothman, K J
通讯作者：
Rothman, K J
影响因子：
--
作者：
Boesgaard TW;Pruhova S;Andersson EA;Cinek O;Obermannova B;Lauenborg J;Damm P;Bergholdt R;Pociot F;Pisinger C;Barbetti F;Lebl J;Pedersen O;Hansen T
通讯作者：
Hansen T
影响因子：
8.2
作者：
Pearson, ER;Pruhova, S;Hattersley, AT
通讯作者：
Hattersley, AT
DOI：
10.1073/pnas.0409177102
发表时间：
2005-03-29
影响因子：
11.1
作者：
Neve, B;Fernandez-Zapico, ME;Froguel, P
通讯作者：
Froguel, P
影响因子：
30.8
作者：
Hattersley, AT;Beards, F;Ellard, S
通讯作者：
Ellard, S