Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium
Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium
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DOI：
10.1007/s00125-019-4906-1
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发表时间：
2019-09-01
期刊：
影响因子：
8.2
通讯作者：
Franks, Paul W.
中科院分区：
文献类型：
--
作者：
Koivula, Robert W.;Forgie, Ian M.;Franks, Paul W.
目的/假设在此，我们描述了创新药物倡议（IMI）糖尿病患者分层研究（DIRECT）流行病学队列在基线和随访检查（18、36和48个月随访）时的特征。方法从24，682名欧洲血统成年人的抽样框架中，在整个欧洲以人群为基础的队列中，使用风险预测算法识别具有不同血液病恶化风险的参与者。（基于年龄、BMI、腰围、抗高血压药物的使用，吸烟状况和父母的2型糖尿病史），并加入前瞻性队列研究（n = 2127）（队列1，前驱糖尿病风险）。我们还从临床登记处招募了6-24个月前诊断为2型糖尿病的患者（n = 789）进入第二个队列研究（队列2，糖尿病）。在基线检查后相似的18个月（两个队列）和相似的48个月（队列1）或相似的36个月（队列2）进行随访检查。使用匹配的方案在北方的七个临床中心对这些队列进行了平行研究。结果使用ADA 2011血糖分类，队列1（糖尿病前期风险）中33%（n = 693）的血糖调节正常，67%（n = 1419）的血糖调节受损。群组1的参与者中有76%为男性。队列1受试者在基线时具有以下特征（平均值+/- SD）：年龄62（6.2）岁; BMI 27.9（4.0）kg/m（2）;空腹血糖5.7（0.6）mmol/l; 2小时血糖5.9（1.6）mmol/l。在最终随访检查时，参与者的临床特征如下：空腹血糖6.0（0.6）mmol/l; 2 h OGTT血糖6.5（2.0）mmol/l。在队列2（糖尿病）中，66%（n = 517）在入组时接受生活方式改变治疗，34%（n = 272）接受二甲双胍加生活方式改变治疗。第二组的参与者中有58%为男性。队列2受试者在基线时具有以下特征：年龄62（8.1）岁; BMI 30.5（5.0）kg/m2;空腹血糖7.2（1.4）mmol/l; 2小时血糖8.6（2.8）mmol/l。在最终随访检查时，参与者的临床特征如下：空腹血糖7.9（2.0）mmol/l; 2小时混合餐耐量试验血糖9.9（3.4）mmol/l。结论/解释IMI DIRECT队列具有强烈的特征，前瞻性评估了各种各样的代谢相关指标。我们预计，通过管理访问提供的队列将为生物标志物发现、多变量病因分析和患者重新分类提供强大的资源，以预防和治疗2型糖尿病。
Aims/hypothesis Here, we describe the characteristics of the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) epidemiological cohorts at baseline and follow-up examinations (18, 36 and 48 months of follow-up). Methods From a sampling frame of 24,682 adults of European ancestry enrolled in population-based cohorts across Europe, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm (based on age, BMI, waist circumference, use of antihypertensive medication, smoking status and parental history of type 2 diabetes) and enrolled into a prospective cohort study (n = 2127) (cohort 1, prediabetes risk). We also recruited people from clinical registries with type 2 diabetes diagnosed 6-24 months previously (n = 789) into a second cohort study (cohort 2, diabetes). Follow-up examinations took place at similar to 18 months (both cohorts) and at similar to 48 months (cohort 1) or similar to 36 months (cohort 2) after baseline examinations. The cohorts were studied in parallel using matched protocols across seven clinical centres in northern Europe. Results Using ADA 2011 glycaemic categories, 33% (n = 693) of cohort 1 (prediabetes risk) had normal glucose regulation and 67% (n = 1419) had impaired glucose regulation. Seventy-six per cent of participants in cohort 1 was male. Cohort 1 participants had the following characteristics (mean +/- SD) at baseline: age 62 (6.2) years; BMI 27.9 (4.0) kg/m(2); fasting glucose 5.7 (0.6) mmol/l; 2 h glucose 5.9 (1.6) mmol/l. At the final follow-up examination the participants' clinical characteristics were as follows: fasting glucose 6.0 (0.6) mmol/l; 2 h OGTT glucose 6.5 (2.0) mmol/l. In cohort 2 (diabetes), 66% (n = 517) were treated by lifestyle modification and 34% (n = 272) were treated with metformin plus lifestyle modification at enrolment. Fifty-eight per cent of participants in cohort 2 was male. Cohort 2 participants had the following characteristics at baseline: age 62 (8.1) years; BMI 30.5 (5.0) kg/m(2); fasting glucose 7.2 (1.4) mmol/l; 2 h glucose 8.6 (2.8) mmol/l. At the final follow-up examination, the participants' clinical characteristics were as follows: fasting glucose 7.9 (2.0) mmol/l; 2 h mixed-meal tolerance test glucose 9.9 (3.4) mmol/l. Conclusions/interpretation The IMI DIRECT cohorts are intensely characterised, with a wide-variety of metabolically relevant measures assessed prospectively. We anticipate that the cohorts, made available through managed access, will provide a powerful resource for biomarker discovery, multivariate aetiological analyses and reclassification of patients for the prevention and treatment of type 2 diabetes.