Heald Adrian, Qin Rui, Williams Richard, Warner-Levy John, Narayanan Ram Prakash, Fernandez Israel, Peng Yonghong, Gibson J Martin, McCay Kevin, Anderson Simon G, Ollier William
Department of Diabetes and Endocrinology, Salford Royal Hospital, Salford Royal NHS Foundation Trust, Salford, UK.
Division of Diabetes, Endocrinology & Gastroenterology, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
Diabetes Ther. 2023 Nov;14(11):1903-1913. doi: 10.1007/s13300-023-01463-9. Epub 2023 Sep 14.
Type 2 diabetes mellitus (T2D) is commonly associated with an increasing complexity of multimorbidity. While some progress has been made in identifying genetic and non-genetic risk factors for T2D, understanding the longitudinal clinical history of individuals before/after T2D diagnosis may provide additional insights.
In this study, we utilised longitudinal data from the DARE (Diabetes Alliance for Research in England) study to examine the trajectory of clinical conditions in individuals with and without T2D. Data from 1932 individuals (T2D n = 1196 vs. matched non-T2D controls n = 736) were extracted and subjected to trajectory analysis over a period of up to 50 years (25 years pre-diagnosis/25 years post-diagnosis). We also analysed the cumulative proportion of people with diagnosed coronary artery disease (CAD) in their general practice (GP) record with an analysis of lower respiratory tract infection (RTI) as a comparator group.
The mean age of diagnosis of T2D was 52.6 (95% confidence interval 52.0-53.4) years. In the years leading up to T2D diagnosis, individuals who eventually received a T2D diagnosis consistently exhibited a considerable increase in several clinical phenotypes. Additionally, immediately prior to T2D diagnosis, a significantly greater prevalence of hypertension (35%)/RTI (34%)/heart conditions (17%)/eye, nose, throat infection (19%) and asthma (12%) were observed. The corresponding trajectory of each of these conditions was much less dramatic in the matched controls. Post-T2D diagnosis, proportions of T2D individuals exhibiting hypertension/chronic kidney disease/retinopathy/infections climbed rapidly before plateauing. At the last follow-up by quintile of disadvantage, the proportion (%) of people with diagnosed CAD was 6.4% for quintile 1 (least disadvantaged) and 11% for quintile 5 (F = 3.4, p = 0.01 for the difference between quintiles).
These findings provide novel insights into the onset/natural progression of T2D, suggesting an early phase of inflammation-related disease activity before any clinical diagnosis of T2D is made. Measures that reduce social inequality have the potential in the longer term to reduce the social gradient in health outcomes reported here.
2型糖尿病（T2D）通常与多种疾病并存的复杂性增加相关。虽然在确定T2D的遗传和非遗传风险因素方面已取得一些进展，但了解个体在T2D诊断之前/之后的纵向临床病史可能会提供更多见解。
在本研究中，我们利用来自英国糖尿病研究联盟（DARE）研究的纵向数据，来检查患有和未患有T2D的个体的临床状况轨迹。提取了1932名个体的数据（T2D组n = 1196，匹配的非T2D对照组n = 736），并在长达50年的时间内（诊断前25年/诊断后25年）进行轨迹分析。我们还分析了其全科医生（GP）记录中被诊断患有冠状动脉疾病（CAD）的人群的累积比例，并将下呼吸道感染（RTI）作为比较组进行分析。
T2D的平均诊断年龄为52.6岁（95%置信区间52.0 - 53.4）。在T2D诊断前的几年中，最终被诊断为T2D的个体在几种临床表型上持续呈现出显著增加。此外，在T2D诊断前，观察到高血压（35%）/RTI（34%）/心脏病（17%）/眼、鼻、喉感染（19%）和哮喘（12%）的患病率显著更高。在匹配的对照组中，这些疾病各自的相应轨迹则没有那么显著。T2D诊断后，患有高血压/慢性肾病/视网膜病变/感染的T2D个体比例在趋于平稳之前迅速攀升。在按劣势程度五分位数进行的最后一次随访中，第1五分位数（最不处于劣势）中被诊断患有CAD的人群比例为6.4%，第5五分位数中为11%（F = 3.4，五分位数之间差异的p值 = 0.01）。
这些发现为T2D的发病/自然进展提供了新的见解，表明在T2D进行任何临床诊断之前存在炎症相关疾病活动的早期阶段。从长远来看，减少社会不平等的措施有可能降低此处报告的健康结果方面的社会梯度。
