Table 1.
Published studies utilizing differentially methylated DNA to interrogate islet β-cell death.
| Study [Ref#] | Technique (Gene) | Subjects Studied (Number of Subjects) | Results |
|---|---|---|---|
| Akirav et al. [23] | qPCR (INS) | T1D subjects, onset within 1.5 yr (17), Healthy control subjects (11) Streptozotocin (STZ)-treated mice, NOD mice |
-Assay can distinguish between islets and other organs - β-cell death in mouse models with increased β-death prior to a decline in insulin content -Increased β-cell death in T1D patients compared to controls |
| Husseiny et al. [40] | qPCR (INS) | No human subjects STZ-treated mice |
-Assay can distinguish between β-cell DNA and other tissues -β-cell death before the rise in blood glucose levels |
| Lebastchi et al. [32] | qPCR (INS) | T1D subjects, onset within 0.6–6 yr (54), Healthy control subjects (19) T1D subjects treated with anti-CD3 monoclonal antibody or placebo (37) |
-Increased β-cell death in T1D subjects compared to control subjects -Teplizumab treatment is associated with reduced level of β-cell death |
| Fisher et al. [41] | qPCR (INS) | No human subjects STZ-treated mice and NOD mice |
-Assay can distinguish between β-cell DNA and other tissues -Increased β-cell death prior to the development of hyperglycemia and decreased β-cell death after increased hyperglycemia |
| Husseiny et al. [28] | qPCR (INS) | Islet transplantation subjects (6), Healthy control subjects (6) NOD mice |
-Increased β-cell death starting at week 10 in NOD mice -Increased β-cell death on day 1 after islet transplantation |
| Usmani-Brown et al. [35] | dPCR (INS) | T1D subjects, onset within 1 yr (43), Relatives of T1D subjects with >2 aAb (26), Health control subjects (27) | -Improved specificity using droplet dPCR -Increased β-cell death in T1D and at-risk subjects compared to controls |
| Herold et al. [39] | dPCR (INS) | At risk subjects (20): T1D progressors (10), Non-progressors (10), High risk subjects (30): Diabetic OGTT (10), Dysglycemia (10), Normal OGTT (10), Islet autotransplantation (4), Control subjects (32) | -β-cell death was associated with decreases in insulin secretion -Detected increased β-cell death in at-risk subjects who progressed to T1D. |
| Fisher et al. [26] | dPCR (INS) | T1D subjects, onset within 48h (32), Obese subjects without diabetes (21) T2D subjects (17), Pediatric control (27), Lean adult control (15) STZ-treated mice, NOD mice |
-β-cell death at T1D onset -No β-cell death detected in T2D or autoimmune disease |
| Lehmann-Werman et al. [36] | DNA Sequencing (INS) | T1D subjects, onset within 1–4 months (11), Islet-graft recipient subjects (10), Pancreatic cancer (42) and pancreatitis (10), Healthy control subjects (31) | -β-cell death at onset of T1D controls |
| Olsen et al. [42] | qPCR (IAPP) | T1D subjects (15), Healthy control subjects (11) NOD mice |
-Detected β-cell death in recent onset T1D subjects |
| Tersey et al. [34] | dPCR (INS) | T1D subjects, onset within 48h (3), Healthy control subjects (3) | -Detected β-cell death in new-onset T1D |
| Bellin et al. [27] | dPCR (INS) | Total pancreatectomy with islet autotransplantation (25), Healthy control subjects (49) | -Decreased β-cell death after pancreatectomy -Increased β-cell death hours after transplantation -Persistent β-cell death predicted greater hyperglycemia at 90 days |
| Sklenarova et al. [43] | dPCR (GCK and INS) | T1D subjects, onset within 4 weeks (25), At risk individuals (14), Healthy control subjects (20) | -Unmethylated GCK DNA was more islet specific than unmethylated INS DNA -Increased β-cell death in autoantibody positive relatives compared with T1D and controls |
| Tersey at al. [22] | dPCR (INS) | No human subjects High and low fat diet-treated mice; STZ-treated mice |
-Episodic levels of β-cell death during obesity |
| Mulukutla et al. [44] | dPCR (INS) | Ketosis prone diabetes (KPD) subjects (112) | -Increased β-cell death in patients with A+ β+ KPD compared to other KPD subtypes -A+ β+ KPD has a slowly progressive β-cell destruction |
| Neyman et al. [37] | dPCR (INS) | T1D subjects, long standing (90), Healthy control subjects (54) | -Increased β-cell death among both C-peptide (−) and C-peptide (+) subjects with longstanding T1D |
| Simmons et al. [45] | dPCR (INS) | At risk subjects (57), Control subjects (165) | -Autoantibodies were associated with increased β-cell death near diabetes onset -Increased β-cell death over time was associated with a younger age of T1D onset |
| Speake et al. [31] | dPCR, DNA Sequencing (INS) | Total pancreatectomy and islet autotransplantation (13), Control subject (1) | -Levels of β-cell death were correlated across different assays |
| Neiman et al. [29] | PCR-DNA Sequencing (INS) | T1D subjects (130), At-risk subjects (32), Healthy control subjects (218) | -No detection of β-cell death in autoantibody-positive subjects at risk for T1D, recent-onset type 1 diabetes or those with long-standing disease |
| Syed et al. [38] | dPCR (INS and CHTOP) | T1D subjects, onset within 48 h (43), At risk subjects (23), T2D subjects (56), Healthy control subjects (10) | -Increased β-cell death in youth with new-onset T1D and healthy autoantibody-negative youth who have first-degree relatives with T1D -Increased β-cell death in youth obese youth compared to lean controls |