Background

Cardiovascular disease is the main determinant of premature mortality in patients with type 1 diabetes. However, time trends regarding different types of cardiovascular disease in childhood-onset type 1 diabetes with a long timespan from the diagnosis of diabetes are not well established. This study aimed to investigate the cumulative incidence of cardiovascular disease in individuals with type 1 diabetes in a population-based cohort in Finland, the country with the world's highest incidence of type 1 diabetes.

Methods

In this retrospective, nationwide registry-based, cohort study, all patients who were diagnosed between Jan 1, 1965, and Dec 31, 1999 with type 1 diabetes when they were younger than 15 years old in Finland were followed up and monitored for the occurrence of cardiovascular disease (including coronary artery disease, stroke, peripheral artery disease, and heart failure) until the end of 2016 and for cardiovascular disease mortality until 2017. Cumulative incidences of cardiovascular disease were calculated by the Fine and Gray method according to the year of diabetes diagnosis using six diagnosis cohorts: 1965–69, 1970–74, 1975–1979, 1980–84, 1985–89, 1990–94, and 1990–95. Trends in cardiovascular disease event rates were analysed by Fine and Gray competing risks regression models using year of diabetes diagnosis as continuous variable. In addition, non-linearity in trends was assessed with restricted cubic splines. The excess risk of coronary artery disease and stroke was estimated by comparison with the risk in the Finnish general population by calculating standardised incidence ratios (SIRs) and their time trends. The data for Finnish general population were drawn from the Cardiovascular Disease Register of the National Institute of Health and Welfare. The SIRs were calculated as ratios of observed and expected number of events in individuals with type 1 diabetes during 1991–2014.

Findings

11 766 individuals were included in this study. During 361 033 person-years of follow-up and a median of 29·6 years (IQR 22·3-37·9) follow-up, a total of 1761 individuals had single or multiple types of cardiovascular disease events. 2686 events (864 [32·2%] coronary artery disease events, of which 663 were acute myocardial infarctions; 497 [18·5%] strokes; 854 [31·8%] peripheral artery diseases, of which 498 were lower extremity amputations; and 471 [17·5%] heart failure events) were reported until Dec 31, 2016, and 1467 deaths until Dec 31, 2017. Cardiovascular disease risk decreased linearly by 3·8% (hazard ratio [HR] 0·96 [95% CI 0·96–0·97]; p<0·0001) by later calendar year of diabetes diagnosis (p<0·0001). There was a decrease in the SIRs for both coronary artery disease and stroke within all 10-year age groups under 65 years, except for stroke in the oldest age group. However, the SIR was still 8·9 (95% CI 3·9–17·5) for coronary artery disease and 2·9 (1·3–5·7) for stroke in those diagnosed with type 1 diabetes in the 1990s. Finally, the cardiovascular disease death rate decreased constantly by diagnosis year.

Interpretation

The risk of cardiovascular disease has decreased over time in Finland in individuals with childhood-onset type 1 diabetes. However, there is still considerable excess cardiovascular disease risk in individuals with type 1 diabetes compared with the general population. These results highlight the need for studies on the mechanisms of atherosclerosis from the time of diagnosis of type 1 diabetes to facilitate early and effective prevention of cardiovascular disease in these individuals.

Funding

Folkhälsan Research Foundation, Academy of Finland, Wilhelm and Else Stockmann Foundation, Liv och Hälsa Society, Novo Nordisk Foundation, Finnish Foundation for Cardiovascular Research, Finnish Diabetes Research Foundation, Diabetes Research Foundation, Medical Society of Finland, Sigrid Jusélius Foundation, and Helsinki University Hospital Research Funds.

中文翻译：

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芬兰 1 型糖尿病患者心血管疾病发病率的长期人群趋势：一项回顾性全国队列研究

背景

心血管疾病是 1 型糖尿病患者过早死亡的主要决定因素。然而，关于儿童期发病的 1 型糖尿病中不同类型心血管疾病的时间趋势与糖尿病诊断的时间跨度尚不明确。本研究旨在调查芬兰人群队列中 1 型糖尿病患者心血管疾病的累积发病率，芬兰是世界上 1 型糖尿病发病率最高的国家。

方法

在这项基于登记的全国性回顾性队列研究中，所有在 1965 年 1 月 1 日至 1999 年 12 月 31 日期间在芬兰被诊断为 15 岁以下的 1 型糖尿病患者都接受了随访并监测了发生情况截至2016年底心血管疾病（包括冠状动脉疾病、脑卒中、外周动脉疾病和心力衰竭）发病率和截至2017年底的心血管疾病死亡率。心血管疾病累计发病率根据发生年份采用精细灰色法计算使用六个诊断队列进行糖尿病诊断：1965-69、1970-74、1975-1979、1980-84、1985-89、1990-94 和 1990-95。使用糖尿病诊断年份作为连续变量，通过 Fine 和 Gray 竞争风险回归模型分析心血管疾病事件发生率的趋势。此外，使用受限三次样条评估了趋势的非线性。通过计算标准化发病率 (SIR) 及其时间趋势，与芬兰一般人群的风险进行比较，从而估计冠状动脉疾病和中风的额外风险。芬兰一般人群的数据来自国家健康和福利研究所的心血管疾病登记册。SIR 计算为 1991-2014 年 1 型糖尿病患者观察到的事件数与预期事件数的比率。芬兰一般人群的数据来自国家健康和福利研究所的心血管疾病登记册。SIR 计算为 1991-2014 年 1 型糖尿病患者观察到的事件数与预期事件数的比率。芬兰一般人群的数据来自国家健康和福利研究所的心血管疾病登记册。SIR 计算为 1991-2014 年 1 型糖尿病患者观察到的事件数与预期事件数的比率。

发现

11766 人被纳入这项研究。在 361 033 人年的随访和中位 29·6 年（IQR 22·3-37·9）的随访期间，共有 1761 人发生单一或多种心血管疾病事件。2686起事件（864起[32·2%]冠状动脉疾病事件，其中663起为急性心肌梗死；497起[18·5%]次中风；854起[31·8%]外周动脉疾病，其中498起为下肢截肢; 和 471 [17·5%] 心力衰竭事件）报告至 2016 年 12 月 31 日，1467 人死亡至 2017 年 12 月 31 日。心血管疾病风险线性下降 3·8%（风险比 [HR] 0·96 [ 95% CI 0·96–0·97]；p<0·0001) 到糖尿病诊断的较晚日历年 (p<0·0001)。在 65 岁以下的所有 10 岁年龄组中，冠状动脉疾病和中风的 SIR 均有所下降，除了最大年龄组的中风。然而，在 1990 年代诊断为 1 型糖尿病的患者中，冠状动脉疾病的 SIR 仍然是 8·9 (95% CI 3·9–17·5)，而中风的 SIR 仍然是 2·9 (1·3–5·7) . 最后，心血管疾病死亡率按诊断年份不断下降。

解释

在芬兰，儿童期发病的 1 型糖尿病患者患心血管疾病的风险随着时间的推移而降低。然而，与一般人群相比，1 型糖尿病患者的心血管疾病风险仍然显着增加。这些结果强调了从诊断 1 型糖尿病开始研究动脉粥样硬化机制的必要性，以促进早期和有效预防这些个体的心血管疾病。

资金

Folkhälsan 研究基金会、芬兰科学院、Wilhelm 和 Else Stockmann 基金会、Liv och Hälsa 协会、诺和诺德基金会、芬兰心血管研究基金会、芬兰糖尿病研究基金会、糖尿病研究基金会、芬兰医学会、Sigrid Jusélius 基金会和赫尔辛基大学医院研究基金。