• F Jansson Sigfrids, E H Dahlström, C Forsblom, N Sandholm, V Harjutsalo, M-R Taskinen, and P-H Groop.
• From the, Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
• J. Intern. Med. 2021 Sep 1; 290 (3): 632-645.

BackgroundWe aimed to assess whether remnant cholesterol concentration and variability predict the progression of diabetic nephropathy (DN) and severe diabetic retinopathy (SDR) in type 1 diabetes.MethodsThis observational prospective study covered 5150 FinnDiane Study participants. Remnant cholesterol was calculated as total cholesterol - LDL cholesterol - HDL cholesterol and variability as the coefficient of variation. DN category was based on consensus albuminuria reference limits and the progression status was confirmed from medical files. SDR was defined as retinal laser treatment. For 1338 individuals, the severity of diabetic retinopathy (DR) was graded using the ETDRS classification protocol. Median (IQR) follow-up time was 8.0 (4.9-13.7) years for DN and 14.3 (10.4-16.3) for SDR.ResultsRemnant cholesterol (mmol L-1 ) was higher with increasing baseline DN category (P < 0.001). A difference was also seen comparing non-progressors (0.41 [0.32-0.55]) with progressors (0.55 [0.40-0.85]), P < 0.001. In a Cox regression analysis, remnant cholesterol predicted DN progression, independently of diabetes duration, sex, HbA1c , systolic blood pressure, smoking, BMI, estimated glucose disposal rate and estimated glomerular filtration rate (HR: 1.51 [1.27-1.79]). Remnant cholesterol was also higher in those who developed SDR (0.47 [0.36-0.66]) than those who did not (0.40 [0.32-0.53]), P < 0.001, and the concentration increased stepwise with increasing DR severity (P < 0.001). Regarding SDR, the HR for remnant cholesterol was 1.52 (1.26-1.83) with the most stringent adjustment. However, remnant cholesterol variability was not independently associated with the outcomes.ConclusionsRemnant cholesterol concentration, but not variability, predicts DN progression and development of SDR. However, it remains to be elucidated whether the associations are causal or not.© 2021 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

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