Metabolic feature-based clustering for subtype identification and longitudinal outcome predictions in the Chinese prediabetic population

Table 1 Baseline characteristics of participants by cluster, mean ± SD/median (interquartile range)

Characteristic	Overall	MOD	MARD	SID	SIR	P value1
Female sex, n (%)	319 (51.4)	81 (45.8)	100 (52.6)	91 (57.2)	47 (49.5)	0.197
Age, years	51.08 ± 10.14	44.04 ± 7.84	57.85 ± 6.82	55.42 ± 7.90	43.39 ± 9.33	< 0.001
Body mass index, kg/m2	25.20 (23.40, 27.40)	25.09 (23.70, 26.50)	25.90 (24.49, 27.38)	23.20 (21.40, 24.60)	29.30 (27.38, 31.90)	< 0.001
Waist circumference, cm	88.80 ± 11.76	86.66 ± 10.55	90.93 ± 10.01	82.24 ± 8.27	98.76 ± 13.74	< 0.001
Systolic blood pressure, mmHg	124.04 ± 15.53	120.68 ± 13.91	127.47 ± 14.45	121.93 ± 17.85	126.81 ± 14.75	< 0.001
Diastolic blood pressure, mmHg	77.91 ± 9.95	77.83 ± 10.02	77.66 ± 9.32	75.81 ± 9.80	81.82 ± 10.25	< 0.001
Fasting glucose, mmol/L	5.96 ± 0.62	5.81 ± 0.66	6.00 ± 0.56	6.07 ± 0.60	5.95 ± 0.65	0.002
2-hour glucose, mmol/L	8.73 ± 1.38	8.61 ± 1.36	8.79 ± 1.38	8.55 ± 1.45	9.15 ± 1.21	0.013
1-hour glucose, mmol/L	11.28 ± 2.20	10.63 ± 2.16	11.54 ± 2.06	11.36 ± 2.42	11.83 ± 1.93	< 0.001
Glycated hemoglobin, %	5.80 ± 0.34	5.51 ± 0.31	5.97 ± 0.23	5.91 ± 0.27	5.84 ± 0.33	< 0.001
Fasting insulin (0 minute)	10.20 (7.21, 14.43)	9.53 (7.50, 11.44)	12.84 (10.12, 15.72)	6.29 (4.84, 7.44)	21.99 (16.79, 27.87)	< 0.001
Insulin (1 hour)	74.77 (47.34, 116.47)	63.24 (45.91, 89.81)	95.61 (65.53, 135.60)	45.57 (32.63, 67.96)	144.85 (99.99, 180.48)	< 0.001
Insulin (2 hours)	72.96 (46.57, 113.40)	65.01 (46.50, 101.10)	91.33 (61.30, 131.45)	45.31 (31.41, 68.39)	154.40 (101.35, 215.55)	< 0.001
HOMA-insulin resistance	2.68 (1.86, 3.89)	2.50 (1.82, 3.06)	3.44 (2.63, 4.32)	1.67 (1.29, 2.08)	5.62 (4.13, 7.56)	< 0.001
HOMA-β cell function	85.71 (58.59, 126.32)	81.12 (64.17, 106.39)	104.34 (83.28, 128.07)	48.66 (37.37, 58.26)	165.29 (134.71, 238.79)	< 0.001
Triglycerides, mmol/L	1.44 (1.04, 2.06)	1.31 (0.96, 2.01)	1.59 (1.19, 2.23)	1.17 (0.90, 1.54)	1.81 (1.32, 2.51)	< 0.001
Total cholesterol, mmol/L	4.81 (4.20, 5.51)	4.75 (4.20, 5.33)	4.78 (4.10, 5.45)	4.90 (4.31, 5.74)	4.78 (4.29, 5.47)	0.248

Sex missing, n = 36 (reported in footnote only).

¹P values: χ² test for categorical variables; Kruskal-Wallis test for continuous variables.

MARD: Mild age-related dysmetabolism; MOD: Mild obesity-related dysmetabolism; SID: Severe insulin deficiency; SIR: Severe insulin resistance; HOMA: Homeostasis model assessment.

Table 2 Cluster-specific dysglycemia transitions and intervention effects: Adjusted hazard ratios and cumulative incidence

Variable	n	Events	Unadjusted 2-year CIF (%)	Adjusted 2-year CIF (%)1	95%CI (adjusted CIF)	aHR2	95%CI3 (aHR)	P value
Progression to diabetes
MARD	104	35	5.8	7.28	4.27-11.10	Reference
MOD	99	17	5.1	3.38	1.70-5.95	0.52	0.29-0.93	0.028a
SID	115	28	7.0	5.20	2.66-8.49	0.84	0.51-1.39	0.496
SIR	49	19	4.1	8.32	4.69-12.84	0.88	0.50-1.57	0.673
Intervention (yes vs no)						0.52	0.30-0.89	0.017a
Sex (male vs female)						1.24	0.82-1.85	0.305
Regression to normoglycemia
MARD	104	11	1.9	3.03	1.41-5.17	Reference
MOD	99	21	7.1	6.49	3.58-10.48	2.08	1.00-4.33	0.049a
SID	115	19	5.2	4.97	2.38-8.28	1.82	0.87-3.84	0.113
SIR	49	9	6.1	5.41	2.09-10.34	1.51	0.63-3.66	0.358
Intervention (yes vs no)						0.63	0.33-1.20	0.159
Sex (male vs female)						0.94	0.56-1.59	0.829
Persistence of prediabetes
MARD	104	58	14.4	15.49	10.99-20.46	Reference
MOD	99	61	14.1	17.50	12.53-22.74	1.18	0.82-1.69	0.380
SID	115	68	22.6	17.21	12.40-22.55	1.25	0.88-1.77	0.222
SIR	49	21	8.2	11.02	6.48-16.28	0.67	0.41-1.11	0.120
Intervention (yes vs no)						0.57	0.40-0.81	0.002a
Sex (male vs female)						0.90	0.68-1.19	0.459

¹Adjusted 2-year cumulative incidence function from Fine-Gray competing risk model with marginal standardization.

²Adjusted hazard ratio from cause-specific Cox models (reference: Mild age-related dysmetabolism, adjusted for intervention and sex).

³95% confidence interval from 500 bootstrap resamples.

^aP < 0.05.

aHR: Adjusted hazard ratio; CIF: Cumulative incidence function; MARD: Mild age-related dysmetabolism; MOD: Mild obesity-related dysmetabolism; SID: Severe insulin deficiency; SIR: Severe insulin resistance; CI: Confidence interval.