Table 1.
Comparison of T2D subgroups identified by representative clinical covariate vs genetic clustering methods.
| Clinical & Biochemical Clustering Ahlqvist et al (6) | Genetic Clustering Udler et al (8) and Mahajan et al (37) | ||||||
|---|---|---|---|---|---|---|---|
| Cluster | Characteristics (6) | Outcomes | Cluster | Characteristics | Outcomes (8) | Example Genes captured in cluster | |
| β-cell | Autoimmune | Autoantibody + ↓ Insulin (plasma) | ↑ insulin dependence | β-cell | ↑ proinsulin, ↓ insulin |
↑ CAD, ↑ stroke |
HNF1A, SLC30A8 |
| Insulin deficiency | ↓ Insulin (plasma) | ↑ Retinopathy, ↑ insulin dependence |
Proinsulin | ↓ insulin, ↓ proinsulin |
- | KCNJ11 | |
| Mixed β-cell + insulin resistance (from (37)) | - | - | - | Mixed | ↓ insulin, ↓ proinsulin, ↑ HOMA2-β |
- | PAM, RREB1 |
| Insulin Resistance | Insulin resistance | ↑ HOMA2-IR, ↑ HOMA2-β |
↑ DKD | Lipodystrophy | ↓ BMI, ↑ insulin, ↑ TG | ↑ CAD, ↑ DKD, ↑ HTN |
KLF14, FAM13A |
| NAFLD/Lipid | ↓ TG | ↓ DKD | TM6SF2, GCKR | ||||
| Obesity | ↑ BMI; mild T2D | - | Obesity/Adiposity | ↑ BMI, ↑insulin | - | FTO/IRX3, MCR4 | |
| ? | Aging | ↑ Age, normal BMI, mild T2D | - | - | - | - | - |
Abbreviations: BMI – body mass index, CAD – coronary artery disease, DKD – diabetic kidney disease, HOMA-β - homeostatic model assessment of pancreatic beta cell function, HOMA2-IR - homeostatic model assessments of insulin resistance, HTN - hypertension, LADA – latent autoimmune diabetes in adults, NAFLD – nonalcoholic fatty liver disease, T1D – type 1 diabetes, TG - triglycerides