Factors associated with the transition from health to disease for type 2 diabetes, cardiovascular disease and kidney dysfunction: A NAKO-IMMEDIATE analysis

Background: Cardio-kidney-metabolic (CKM) diseases share risk factors, but their shared and distinct risk factors for disease progression remain unclear. We examined whether classical risk factors predict baseline CKM indicators and their longitudinal changes in a population-based German National Cohort (NAKO) sample. Methods: In 2,650 NAKO-IMMEDIATE participants selected for deep-phenotyping, baseline values and 5-year changes in glycated hemoglobin (HbA1c), systolic blood pressure (SBP), pulse wave velocity (PWV), and estimated glomerular filtration rate (eGFR) were linearly regressed on age, sex, education, alcohol and tobacco consumption, body mass index (BMI), and residuals of BMI-adjusted waist circumference (WC) with mutual adjustment. Results: Baseline values for HbA1c were 34.6{+/-}5.8 mmol/mol, for PWV 8.3{+/-}1.5 m/s, for SBP 128.0{+/-}15.7 mmHg and for eGFR 96.0{+/-}14.6 ml/min/1.73 m2. Cross-sectionally, all risk factors were associated with one or more of the CKM indicators, with age and BMI being associated with all four indicators. Over 5 years, HbA1c (1.2{+/-}4.2 mmol/mol), PWV (0.5{+/-}1.2 m/s) and SBP (0.6{+/-}14.2 mmHg) increased, whereas eGFR (-2.3{+/-}9.5 ml/min/1.73 m2) decreased. Age (0.03 m/s per 5 year, 95% CI 0.01, 0.06 m/s) was associated with higher and BMI (-0.02 m/s per 1kg/m2, -0.03, -0.01) with lower PWV changes. No other risk factors were associated with CKM indicator changes. Conclusion: Classical risk factors were more frequently related to baseline CKM indicators than to their 5-year changes. Within longitudinal analyses, only age and BMI were related to PWV 5-year changes. Keywords: Cardio-kidney-metabolic function, risk factors, longitudinal studies