Cluster-based metabolic subphenotypes and projected cross-organ risk in Chinese adults with prediabetes

Figure 1 Distributions of continuous risk-score-derived organ-risk measures across metabolic subtypes. A: Cardiovascular disease 10-year risk; B: Chronic kidney disease (CKD) risk probability; C: Fibrosis-4 (FIB-4) index. Violin plots show the subtype-specific distributions of Framingham-estimated 10-year cardiovascular disease (CVD) risk, CKD prognosis consortium-estimated projected 5-year CKD risk, and FIB-4 index among adults with prediabetes assigned to four metabolic subtypes. Embedded box plots indicate the interquartile range, whiskers extend to 1.5 × interquartile range, and white circles indicate medians. The continuous distributions differed across subtypes for all three measures by Kruskal-Wallis test (all P < 0.001). Higher values indicate greater risk-score-derived CVD risk, projected CKD risk, or FIB-4-defined liver fibrosis-risk signal. CVD risk was analyzed in 452 participants, projected CKD risk in 448 participants, and FIB-4 in 621 participants. CVD: Cardiovascular disease; CKD: Chronic kidney disease; FIB-4: Fibrosis-4; MARD: Mild age-related dysmetabolism; MOD: Mild obesity-related dysmetabolism; SID: Severe insulin deficiency; SIR: Severe insulin resistance.

Figure 2 Within-subtype prevalence and source contribution of threshold-defined intermediate/high-risk status across metabolic subtypes. A: It shows the percentage of participants within each metabolic subtype who met the primary analytic threshold for each risk-score-derived measure; B: It shows the proportion of all threshold-positive participants accounted for by each subtype for the same measure. Primary analytic thresholds were defined as Framingham-estimated 10-year cardiovascular disease risk ≥ 10%, chronic kidney disease (CKD) prognosis consortium-estimated projected 5-year CKD risk ≥ 5%, and fibrosis-4 (FIB-4) index ≥ 1.30. The corresponding threshold-positive counts were 131 of 452 participants for cardiovascular disease risk, 117 of 448 participants for projected CKD risk, and 152 of 621 participants for FIB-4. Percentages are rounded to one decimal place and may not sum exactly to 100.0%. These categories represent score-defined intermediate/high-risk status and FIB-4-defined liver fibrosis-risk signal, not observed incident cardiovascular, kidney, or liver events. CVD: Cardiovascular disease; CKD: Chronic kidney disease; FIB-4: Fibrosis-4; MARD: Mild age-related dysmetabolism; MOD: Mild obesity-related dysmetabolism; SID: Severe insulin deficiency; SIR: Severe insulin resistance.

Figure 3 Prevalence ratios for threshold-defined intermediate/high-risk status across metabolic subtypes. Forest plot shows prevalence ratios (PRs) and 95%CIs for the association between metabolic subtype and each threshold-defined risk-score-derived outcome, with mild obesity-related dysmetabolism as the reference group. Model 1 was unadjusted. Model 2 used outcome-specific adjusted covariates that were not direct components of the corresponding target risk equation: (1) Triglyceride (TG), aspartate aminotransferase, platelet count, estimated glomerular filtration rate, low-density lipoprotein cholesterol (LDL-C), and waist circumference for cardiovascular disease risk; (2) Aspartate aminotransferase, platelet count, TG, LDL-C, and waist circumference for projected chronic kidney disease (CKD) risk; and (3) Waist circumference, sex, TG, estimated glomerular filtration rate, LDL-C, and systolic blood pressure for fibrosis-4 (FIB-4). PRs greater than 1 indicate a higher prevalence of threshold-positive status relative to mild obesity-related dysmetabolism. 95%CIs crossing 1 indicate that the comparison did not reach statistical significance at the two-sided 0.05 level. The adjusted-model analytic samples included 452 participants for Framingham-estimated 10-year cardiovascular disease risk ≥ 10%, 448 participants for CKD prognosis consortium-estimated projected 5-year CKD risk ≥ 5%, and 585 participants for FIB-4 ≥ 1.30. Estimates describe score-derived projected risk categories and FIB-4-defined liver fibrosis-risk signal rather than observed incident cardiovascular, kidney, or liver outcomes. CVD: Cardiovascular disease; CKD: Chronic kidney disease; FIB-4: Fibrosis-4; MARD: Mild age-related dysmetabolism; MOD: Mild obesity-related dysmetabolism; SID: Severe insulin deficiency; SIR: Severe insulin resistance; Ref: Reference.