AUTHOR=Chan Kam Wa , Chow Tak Yee , Yu Kam Yan , Xu Yulong , Zhang Nevin Lianwen , Wong Vivian Taam , Li Saimei , Tang Sydney Chi Wai 

TITLE=SYmptom-Based STratification of DiabEtes Mellitus by Renal Function Decline (SYSTEM): A Retrospective Cohort Study and Modeling Assessment

JOURNAL=Frontiers in Medicine

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.682090

DOI=10.3389/fmed.2021.682090

ISSN=2296-858X

ABSTRACT=Background
Previous UK Biobank studies showed that symptoms and physical measurements had excellent prediction on long-term clinical outcomes in general population. Symptoms and signs could intuitively and non-invasively predict and monitor disease progression, especially for telemedicine, but related research is limited in diabetes and renal medicine. 

Methods
This retrospective cohort study aimed to evaluate the predictive power of a symptom-based stratification framework and individual symptoms for diabetes. 302 adult diabetes patients were consecutively sampled from outpatient clinics in Hong Kong for prospective symptom assessment. Demographics and longitudinal measures of biochemical parameters were retrospectively extracted from linked medical records. The association between estimated glomerular filtration rate (GFR) (independent variable) and biochemistry, epidemiological factors and individual symptoms was assessed by mixed regression analyses. A symptom-based stratification framework of diabetes using symptom clusters was formulated by Delphi consensus method. Akaike information criterion (AIC) and Bayesian information criterion (BIC) were compared between statistical models with different combinations of biochemical, epidemiological and symptom variables. 

Results
In the 4.2-year follow-up period, edema (-1.8 ml/min/1.73m2, 95%CI: -2.5 to -1.2, p<0.001), epigastric bloating (-0.8 ml/min/1.73m2, 95%CI: -1.4 to -0.2, p=0.014) and alternating dry and loose stool (-1.1 ml/min/1.73m2, 95%CI: -1.9 to -0.4, p=0.004) were independently associated with faster annual GFR decline. 11 symptom clusters were identified from literature, stratifying diabetes predominantly by gastrointestinal phenotypes. Using symptom clusters synchronized by Delphi consensus as the independent variable in statistical models reduced complexity and improved explanatory power when compared to using individual symptoms. Symptom-biologic-epidemiologic combined model had the lowest AIC (4478 vs 5824 vs 4966 vs 7926) and BIC (4597 vs 5870 vs 5065 vs 8026) compared to the symptom, symptom-epidemiologic and biologic-epidemiologic models, respectively. Patients co-presenting with a constellation of fatigue, malaise, dry mouth and dry throat were independently associated with faster annual GFR decline (1.1 ml/min/1.73m2, 95%CI: -0.2 to -0.0, p=0.011). 

Conclusions
Add-on symptom-based diagnosis improves the predictive power on renal function decline among diabetic patients based on key biochemistry and epidemiological factors.