Harjutsalo Valma, Kallio Milla, Forsblom Carol, Groop Per-Henrik
Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland.
Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Lancet Reg Health Eur. 2023 Feb 13;28:100594. doi: 10.1016/j.lanepe.2023.100594. eCollection 2023 May.
The prevalence, incidence and risk factors and especially the effect of diabetic nephropathy (DN) and diabetic retinopathy on the risk of chronic limb threatening ischemia (CLTI) have been sparsely studied in individuals with type 1 diabetes (T1D).
The prospective cohort study consisted of 4697 individuals with T1D from the nationwide Finnish Diabetic Nephropathy (FinnDiane) Study. Medical records were thoroughly reviewed in order to ascertain all CLTI events. The key risk factors were DN and severe diabetic retinopathy (SDR).
There were 319 events of confirmed CLTI, 102 prevalent events at baseline and 217 incident events during the follow-up of 11.9 (IQR 9.3-13.8) years. The 12-year cumulative incidence of CLTI was 4.6% (95% CI 4.0-5.3). Risk factors included presence of DN, SDR, age, duration of diabetes, HbA, systolic blood pressure, triglycerides and current smoking. Sub-hazard ratios (SHRs) according to combinations of DN status and presence (+) or absence (-) of SDR were 4.8 (2.0-11.7) for normoalbuminuria/SDR+, 3.2 (1.1-9.4) for microalbuminuria/SDR-, 11.9 (5.4-26.5) for microalbuminuria/SDR+, 8.7 (3.2-23.2) for macroalbuminuria/SDR-, 15.6 (7.4-33.0) for macroalbuminuria/SDR+ and 37.9 (17.2-78.9) for kidney failure compared with individuals with normal albumin excretion rate and without SDR.
Diabetic nephropathy, especially kidney failure, is associated with high risk of limb threatening ischemia in individuals with T1D. The risk of CLTI increases gradually according to the severity of diabetic nephropathy. Also, diabetic retinopathy is independently and additively associated with high risk of CLTI.
This research was funded by grants from Folkhälsan Research Foundation, Academy of Finland (316664), Wilhelm and Else Stockmann Foundation, Liv och Hälsa Society, Novo Nordisk Foundation (NNF OC0013659), Finnish Foundation for Cardiovascular Research, Finnish Diabetes Research Foundation, Medical Society of Finland, Sigrid Jusélius Foundation and Helsinki University Hospital Research Funds.
1型糖尿病（T1D）患者中糖尿病肾病（DN）和糖尿病视网膜病变对慢性肢体威胁性缺血（CLTI）风险的患病率、发病率、危险因素，尤其是其影响，研究较少。
这项前瞻性队列研究纳入了来自芬兰全国糖尿病肾病（FinnDiane）研究的4697例T1D患者。为确定所有CLTI事件，对病历进行了全面审查。关键危险因素为DN和重度糖尿病视网膜病变（SDR）。
在11.9（四分位间距9.3 - 13.8）年的随访期间，共发生319例确诊的CLTI事件，基线时102例为现患事件，217例为新发事件。CLTI的12年累积发病率为4.6%（95%置信区间4.0 - 5.3）。危险因素包括DN的存在、SDR、年龄、糖尿病病程、糖化血红蛋白、收缩压、甘油三酯和当前吸烟情况。根据DN状态以及SDR存在（+）或不存在（-）的组合计算的亚危险比（SHR），与白蛋白排泄率正常且无SDR的个体相比，正常白蛋白尿/SDR+为4.8（2.0 - 11.7），微量白蛋白尿/SDR-为3.2（1.1 - 9.4），微量白蛋白尿/SDR+为11. 9（5.4 - 26.5），大量白蛋白尿/SDR-为8.7（3.2 - 23.2），大量白蛋白尿/SDR+为15.6（7.4 - 33.0），肾衰竭为37.9（17.2 - 78.9）。
糖尿病肾病，尤其是肾衰竭，与T1D患者肢体威胁性缺血的高风险相关。CLTI的风险根据糖尿病肾病的严重程度逐渐增加。此外，糖尿病视网膜病变与CLTI的高风险独立且叠加相关。
本研究由芬兰健康基金会、芬兰科学院（316664）、威廉和埃尔丝·斯托克曼基金会、生命与健康协会、诺和诺德基金会（NNF OC0013659）、芬兰心血管研究基金会、芬兰糖尿病研究基金会、芬兰医学协会、西格丽德·尤塞利乌斯基金会以及赫尔辛基大学医院研究基金提供资助。
