Dietary macronutrients, macronutrient substitutions, and the risk of cardio-renal-metabolic multimorbidity: a prospective cohort study

Cardio-renal–metabolic multimorbidity (CRMM), defined as the coexistence of at least two of cardiovascular disease, chronic kidney disease, and type 2 diabetes, is a growing public health concern. Dietary macronutrients play an important role in the management of diet-related chronic diseases. We aimed to investigate the association between macronutrient intake and CRMM risk, as well as the substitution of dietary macronutrients in relation to that risk. In this prospective cohort study, 2,539 adults (mean age 40.9 ± 13.5 years; BMI 27.1 ± 4.8 kg/m²) from the Tehran Lipid and Glucose Study were followed for a median of 11.6 years. Macronutrient intake was assessed using a validated 168-item food-frequency questionnaire. Cox models estimated hazard ratios (HRs) for CRMM across tertiles of macronutrient intake, as well as for macronutrient substitution in relation to CRMM risk, adjusting for demographic and lifestyle factors. During follow-up, 216 participants developed CRMM. Participants in the highest tertile of carbohydrate, fat and SFA intake had a higher risk of CRMM after adjustment for confounding factors (carbohydrate HR: 1.74, 95% CI: 1.23–2.47, P for trend = 0.005; fat HR: 1.77, 95% CI: 1.24–2.51, P for trend = 0.005; SFA HR: 1.86, 95% CI: 1.29–2.67, P for trend = 0.002) compared with those in the lowest tertile. In contrast, participants in the highest tertile of protein, MUFA and PUFA intake had a lower risk of CRMM after adjustment for confounding factors (protein HR: 0.69, 95% CI: 0.48–1.00, P for trend = 0.008; MUFA HR: 0.50, 95% CI: 0.35–0.71, P for trend < 0.001; PUFA HR: 0.60, 95% CI: 0.43–0.84, P for trend = 0.007, respectively) compared with those in the lowest tertile. Substituting carbohydrates with protein (HR: 0.97; 95% CI: 0.95–0.99), MUFA (HR: 0.95; 95% CI: 0.93–0.98), and PUFA (HR: 0.96; 95% CI: 0.95–0.99) was associated with a lower risk of CRMM. Substituting protein for carbohydrate (HR: 1.11; 95% CI: 1.03–1.17) was associated with a higher risk of CRMM. Replacing total fat with protein (HR: 0.96; 95% CI: 0.94–0.97) was also associated with a lower risk of CRMM. Finally, replacing SFA with MUFA (HR: 0.95; 95% CI: 0.94–0.97) and PUFA (HR: 0.94; 95% CI: 0.93–0.97) was associated with a lower risk of CRMM. In conclusion, reducing carbohydrates and total dietary fat, along with replacing them with protein, may be associated with reduced risk of CRMM. Likewise, substituting carbohydrates and SFA with MUFA and PUFA may be associated with decreased CRMM risk. Not applicable.