Table 2 Summary of published studies using complex approaches to type 2 diabetes classification.
From: Precision subclassification of type 2 diabetes: a systematic review
Approach Total n % Female Mean age/age range | % Race/ethnicity breakdown | % Prevalent or new onset T2D, n (%) % Prospective or Cross sectional, n (%) | Machine learning approach | T2D subclassified Groups identified | Outcome category, n (%) | Overall quality, n (%) | References |
---|---|---|---|---|---|---|---|
Complex: Ahlqvist and directly replicated Ahlqvist clusters (22 studies) n = 88,197 43% female 55.3 years | 81% Non-Hispanic White, 11% East Asian, 4% Hispanic, 3% South Asian, <1% Black, <1% Other | Prevalent (n = 11, 50%), New onset (n = 11, 50%) Longitudinal (n = 8, 36.6%), Cross-sectional (n = 14, 63.6%) | 100% k-means | SAID, SIDD, SIRD, MOD, MARD | Microvascular & macrovascular events (n = 9, 41%), Clinical and biochemical traits (n = 4, 18%) Microvascular events only (n = 3, 13%), Glycaemia (n = 2, 9%), Macrovascular events only (n = 1, 5%), omic (n = 1, 5%), Other (n = 2, 9%) | Very Low (n = 1, 5%), Low (n = 3, 13%), Moderate (n = 18, 82%) | 8,40,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108 |
Complex: Similar to Ahlqvist clusters (13 studies) n = 214,093 45% female 58.6 years | 72% Non-Hispanic White, 12% Hispanic, 10% South Asian, 4% East Asian, 2% Black, <1% Native American, <1% Other | Prevalent (n = 11, 85%), New onset (n = 2, 15%) Longitudinal (n = 7, 54%), Cross sectional (n = 6, 46%) | a) Addition of complementary clinical variables (i.e., HDL, TG, waist circumference, uric acid, etc.) b) Incorporating new clustering, i.e., self-normalising neural networks trained on k-means clustering. c) Addition of ethnic-specific thresholds for BMI. | SAID, SIDD, SIRD, MOD, and MARD. Five clusters: Older onset, Severe hyperglycaemia, Severe obesity, Younger Onset, and Insulin use. Four clusters: 42% (older onset), 14% (poor glucose control), 24% (severe obesity), and 20% (younger-onset). New subgroups MD, EOIDD, EOIRD, LOIDD, LOIRD. | Microvascular & macrovascular (n = 5, 38%), Microvascular events only (n = 3, 23%), Macrovascular events (n = 1, 8%), Glycaemia (n = 1, 8%), Other (n = 3, 23%) | Very Low (n = 1, 8%), Low (n = 5, 38%) Moderate (n = 7, 54%) | |
Complex: Simple clinical features (4 studies) n = 22,296 46.5% female 56 years | 34% Non-Hispanic White, 25% Asian, 25% Middle Eastern, 9% Black, 5% Hispanic, 1% Native American/American Indian/Alaskan Native, <1% Other | Prevalent T2D (n = 3, 75%), New onset (n = 1, 25%) Longitudinal (n = 3, 75%), Cross-sectional (n = 1, 25%) | 50% k-means (n = 2), 50% other (n = 2) | variable | Mortality (n = 2, 50%), Cardiovascular events (n = 1, 25%), Clinical and biochemical traits (n = 1, 25%) | Moderate (n = 3, 75%), Low (n = 1, 25%) | |
Complex: Complex clinical features (11 studies) n = 386,889 46.8% female 60 years | 57% Non-Hispanic White, 24% Asian, 8% Black, 6% Hispanic, <5% Other | Prevalent T2D (n = 9, 82%), New onset (n = 2, 18%) Longitudinal (n = 7, 64%), Cross-sectional (n = 4, 36%) | variable | variable | Cardiovascular events (n = 4, 36%), Glycaemic control (n = 3, 27%), Complications other than CVD event (n = 2, 18%), Mortality (n = 1, 9%), Other (n = 1, 9%) | Moderate (n = 9, 82%), Low (n = 2, 18%) | |
Complex: Cardiovascular features (2 studies) n = 974 55.4% female 63 years | 100% Non-Hispanic White | Prevalent T2D (n = 2, 100%) Longitudinal (n = 2, 100%) | Factor analysis (clustering) (n = 1, 50%), Hierarchical clustering (n = 1, 50%) | 3 and 4 clusters | Cardiovascular death and events (n = 2, 100%) | Moderate (n = 1, 50%), Low (n = 1, 50%) | |
Complex: Behavioural features (2 studies) n = 653 40.5% female 63.5 years | 48% Non-Hispanic White, 50% Asian, 2% others | Prevalent (n = 1, 50%), New onset (n = 1, 50%) Longitudinal (n = 1, 50%), Cross sectional (n = 1, 50%) | clustering, hierarchical clustering | 2 and 4 clusters | Glycaemic control (n = 2, 100%) | Moderate (n = 1, 50%), Low (n = 1, 50%) | |
Complex: Glycemic features (4 studies) n = 67,064 42.8% female 62.5 years | 40.6% Non-Hispanic White, 25% Asian, 25% Middle Eastern, 9.4% Other | Prevalent (n = 3, 75%), New onset (n = 1, 25%) Longitudinal (n = 3, 75%), Cross sectional (n = 1, 25%) | 50% k-means, 25% latent-class analysis, 25% hierarchical clustering | 3 and 4 clusters | Glycaemic control (n = 2, 50%), Cardiovascular events (n = 2, 50%) | Moderate (n = 3, 75%), Very low (n = 1, 25%) | |
Complex: Genetics (3 studies) n = 42,952 | 100% Non-Hispanic White | Prevalent T2D (n = 3, 100%) Cross sectional (n = 3, 100%) | Bayesian Non-negative Matrix Factorisation (n = 2, 67%), Hierarchical clustering (n = 1, 33%) | 5 clusters of variant-trait associations; 3 clusters of skeletal dysregulated genes/pathways in people with diabetes | Coronary artery disease, stroke, renal disease | Moderate (n = 2, 67%), Low (n = 1, 33%) | |
Complex: Hormonal (1 study) n = 96 participants 53% female 62 years | 100% Non-Hispanic White | New onset (n = 1, 100%) Cross sectional (n = 1, 100%) | Two-step cluster analysis using log-likelihood distance measures | Two clusters (cluster 1: low GLP-1 and Ghrelin; cluster 2: high GLP-1 and Ghrelin) | Glycemia (n = 1, 100%) | Moderate (n = 1, 100%) |