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. 2025 Jun 27;26(13):6227.
doi: 10.3390/ijms26136227.

The Interplay of Cardiometabolic Syndrome Phenotypes and Cardiovascular Risk Indices in Patients Diagnosed with Diabetes Mellitus

Daniela Denisa Mitroi Sakizlian  1 , Lidia Boldeanu  2 , Adina Mitrea  3 , Diana Clenciu  3 , Ionela Mihaela Vladu  3 , Alina Elena Ciobanu Plasiciuc  4 , Andra Veronica Șarla  1 , Isabela Siloși  5 , Mihail Virgil Boldeanu  5 , Mohamed-Zakaria Assani  1   5 , Daniela Ciobanu  6
Affiliations

The Interplay of Cardiometabolic Syndrome Phenotypes and Cardiovascular Risk Indices in Patients Diagnosed with Diabetes Mellitus

Daniela Denisa Mitroi Sakizlian et al. Int J Mol Sci. .

Abstract

Metabolic syndrome (MetS) and its associated cardiometabolic phenotypes significantly contribute to the global burden of cardiovascular disease (CVD), especially in individuals with type 2 diabetes mellitus (T2DM) and prediabetes. This study aimed to explore the association between cardiometabolic phenotypes-specifically, metabolically unhealthy normal weight (MUHNW) and metabolically unhealthy obese (MUHO)-and various cardiovascular risk indices including the triglyceride-glucose (TyG) index and its derivatives, the atherogenic index of plasma (AIP), the cardiometabolic index (CMI), and the cardiac risk ratio (CRR). A total of 300 participants were evaluated (100 with prediabetes and 200 with T2DM). Anthropometric, biochemical, and lifestyle parameters were assessed and stratified across phenotypes. The results demonstrated that cardiovascular risk indices were significantly elevated in the MUHO compared to MUHNW phenotypes, with T2DM patients consistently exhibiting higher risk profiles than their prediabetic counterparts. TyG-derived indices showed strong correlations with BMI, waist-hip ratio (WHR), waist-height ratio (WHtR), and body fat percentage (%BF). The findings suggest that cardiometabolic phenotypes are more strongly associated with elevated cardiometabolic risk indices than body weight alone. These indices may enhance early risk stratification and intervention efforts. The study investigates the association of cardiometabolic phenotypes with surrogate cardiovascular risk indices, not direct CVD outcomes, However, the cross-sectional design and population homogeneity limit the generalizability of the results and preclude causal inference.

Keywords: atherogenic index of plasma; cardiometabolic phenotypes; cardiometabolic risk; cardiovascular risk; metabolic syndrome; prediabetes; triglyceride-glucose index; type 2 diabetes mellitus.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Representation of the distribution of different MetS-related indices for MUHNW and MUHO phenotypes for PreDM and T2DM patients for the following: TyG-WHtR (A), %BF (B), TG/HDL-c (C), AIP (D), CMI (E), and CRR (F).
Figure 2
Figure 2
Correlation matrix between glycemic spectrum, lipid spectrum, anthropometric indices, and metabolic syndrome-related indices in the PreDM cohort. The correlation heatmap illustrates the relationships between the measured indicators. Strong positive correlations are represented by intense purple, while strong negative correlations are depicted in bright blue.
Figure 3
Figure 3
Correlation matrix between glycemic spectrum, lipid spectrum, anthropometric indices, and metabolic syndrome-related indices in the T2DM cohort. The correlation heatmap illustrates the relationships between the measured indicators. Strong positive correlations are represented by intense purple, while strong negative correlations are depicted in bright blue.
Figure 4
Figure 4
Correlation matrix between anthropometric indices and metabolic syndrome-related indices in the PreDM cohort, classified in the MUHNW phenotype. The correlation heatmap illustrates the relationships between the measured indicators. Strong positive correlations are represented by intense purple, while strong negative correlations are depicted in bright blue.
Figure 5
Figure 5
Correlation matrix between anthropometric indices and metabolic syndrome-related indices in the PreDM cohort, classified in the MUHO phenotype. The correlation heatmap illustrates the relationships between the measured indicators. Strong positive correlations are represented by intense purple, while strong negative correlations are depicted in bright blue.
Figure 6
Figure 6
Correlation matrix between anthropometric indices and metabolic syndrome-related indices in the T2DM cohort, classified in the MUHNW phenotype. The correlation heatmap illustrates the relationships between the measured indicators. Strong positive correlations are represented by intense purple, while strong negative correlations are depicted in bright blue.
Figure 7
Figure 7
Correlation matrix between anthropometric indices and metabolic syndrome-related indices in the T2DM cohort, classified in the MUHO phenotype. The correlation heatmap illustrates the relationships between the measured indicators. Strong positive correlations are represented by intense purple, while strong negative correlations are depicted in bright blue.
Figure 8
Figure 8
Representation of the comparison of MetS-related indices between male and female cohorts: TyG values for both PreDM and T2DM cohorts separated for male and female (A), %BF values for both PreDM and T2DM cohorts separated for male and female (B), TG/HDL-c ratio values for both PreDM and T2DM cohorts separated for male and female (C), TyG-BMI values for both PreDM and T2DM cohorts separated for male and female (D), TyG-WC values for both PreDM and T2DM cohorts separated for male and female (E), TyG-WHtR values for both PreDM and T2DM cohorts separated for male and female (F), AIP values for both PreDM and T2DM cohorts separated for male and female (G), CMI values for both PreDM and T2DM cohorts separated for male and female (H), and CRR values for both PreDM and T2DM cohorts separated for male and female (I).
Figure 8
Figure 8
Representation of the comparison of MetS-related indices between male and female cohorts: TyG values for both PreDM and T2DM cohorts separated for male and female (A), %BF values for both PreDM and T2DM cohorts separated for male and female (B), TG/HDL-c ratio values for both PreDM and T2DM cohorts separated for male and female (C), TyG-BMI values for both PreDM and T2DM cohorts separated for male and female (D), TyG-WC values for both PreDM and T2DM cohorts separated for male and female (E), TyG-WHtR values for both PreDM and T2DM cohorts separated for male and female (F), AIP values for both PreDM and T2DM cohorts separated for male and female (G), CMI values for both PreDM and T2DM cohorts separated for male and female (H), and CRR values for both PreDM and T2DM cohorts separated for male and female (I).
Figure 9
Figure 9
Receiver operating characteristic (ROC) curve for %BF PreDM—DM (A), %BF PreDM-MUHNW—DM-MUHNW (B), %BF PreDM-MUHO—DM-MUHO (C), WHtR PreDM—DM (D), WHtR PreDM-MUHNW—DM-MUHNW (E), WHtR PreDM-MUHO—DM-MUHO (F), TyG-WHtR PreDM—DM (G), TyG-WHtR PreDM-MUHNW—DM-MUHNW (H), TyG-WHtR PreDM-MUHO—DM-MUHO (I), TG/HDL-c PreDM—DM (J), TG/HDL-c PreDM-MUHNW—DM-MUHNW (K), TG/HDL-c PreDM-MUHO—DM-MUHO (L), AIP PreDM—DM (M), AIP PreDM-MUHNW—DM-MUHNW (N), AIP PreDM-MUHO—DM-MUHO (O), CMI PreDM—DM (P), CMI PreDM-MUHNW—DM-MUHNW (Q), CMI PreDM-MUHO—DM-MUHO (R), CRR PreDM—DM (S), CRR PreDM-MUHNW—DM-MUHNW (T), and CRR PreDM-MUHO—DM-MUHO (U).
Figure 9
Figure 9
Receiver operating characteristic (ROC) curve for %BF PreDM—DM (A), %BF PreDM-MUHNW—DM-MUHNW (B), %BF PreDM-MUHO—DM-MUHO (C), WHtR PreDM—DM (D), WHtR PreDM-MUHNW—DM-MUHNW (E), WHtR PreDM-MUHO—DM-MUHO (F), TyG-WHtR PreDM—DM (G), TyG-WHtR PreDM-MUHNW—DM-MUHNW (H), TyG-WHtR PreDM-MUHO—DM-MUHO (I), TG/HDL-c PreDM—DM (J), TG/HDL-c PreDM-MUHNW—DM-MUHNW (K), TG/HDL-c PreDM-MUHO—DM-MUHO (L), AIP PreDM—DM (M), AIP PreDM-MUHNW—DM-MUHNW (N), AIP PreDM-MUHO—DM-MUHO (O), CMI PreDM—DM (P), CMI PreDM-MUHNW—DM-MUHNW (Q), CMI PreDM-MUHO—DM-MUHO (R), CRR PreDM—DM (S), CRR PreDM-MUHNW—DM-MUHNW (T), and CRR PreDM-MUHO—DM-MUHO (U).
Figure 10
Figure 10
Conceptual framework of study design and analytical workflow. Distribution of the patients after the cardiometabolic phenotypes.
See this image and copyright information in PMC

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