TABLE 2

Predictive characteristics (sensitivity, specificity, PPV, NPV, +LR, −LR, and cumulative disease risk) of the four diabetes-associated autoantibodies (DAAs, ICAs, IAAs, and GADAs, and IA-2A)

Combinations of DAAType 1 diabetes/allSensitivitySpecificityPPVNPV+LR−LRCumulative risk
Total number of subjects (n)180/7,410
ICA (the only positive DAA)1/7820.6 (0–3.1)89.2 (88.5–89.9)0.1 (0.0–0.7)97.3 (96.9–97.7)0.1 (0.0–0.3)1.1 (1.1–1.1)0.3 (0–0.8)
Double positivity*14/1287.8 (4.3–12.7)98.4 (98.1–98.7)10.9 (6.1–17.7)97.7 (97.4–98.1)4.9 (2.9–8.3)0.9 (0.9–1.0)16.0 (7.4–24.6)
ICA, IAA10/565.6 (2.7–10.0)99.4 (99.2–99.5)17.9 (8.9–30.4)97.7 (97.3–98.0)8.7 (4.5–16.7)1.0 (0.9–1.0)24.9 (9.8–40.0)
ICA, GADA2/601.1 (0.1–4.0)99.2 (99.0–99.4)3.3 (0.4–11.5)97.6 (97.2–97.9)1.4 (0.4–5.0)1.0 (1.0–1.0)4.4 (0–10.5)
ICA, IA-2A2/121.1 (0.1–4.0)99.9 (99.7–99.9)16.7 (2.1–48.4)97.6 (97.2–97.9)8.0 (2.0–32.3)1.0 (1.0–1.0)25.0 (0–55.0)
Triple positivity*42/8723.3 (17.4–30.2)99.4 (99.2–99.5)48.3 (37.4–59.2)98.1 (97.8–98.4)37.5 (25.4–55.2)0.8 (0.7–0.8)66.7 (52.8–80.7)
ICA, IAA, GADA15/368.3 (4.7–13.4)99.7 (99.6–99.8)41.7 (25.5–59.2)97.8 (97.4–98.1)28.7 (15.2–54.1)0.9 (0.9–0.9)54.2 (33.3–75.1)
ICA, IAA, IA-2A20/2711.1 (6.9–16.6)99.9 (99.8–100)74.1 (53.7–88.9)97.8 (97.5–98.2)114.8 (50.5–262.7)0.9 (0.9–0.9)84.7 (69.2–100)
ICA, GADA, IA-2A7/243.9 (1.6–7.8)99.8 (99.6–99.9)29.2 (12.6–51.1)97.7 (97.3–98.0)16.5 (7.1–38.3)1.0 (0.9–1.0)41.5 (17.4–65.5)
All four DAA positive98/17654.4 (46.9–61.9)98.9 (98.7–99.1)55.7 (48.0–63.2)98.9 (98.6–99.1)50.5 (39.5–63.9)0.5 (0.4–0.5)76.5 (66.0–87.1)
Positive for at least ICA155/1,17386.1 (80.2–90.8)85.9 (85.1–86.7)13.2 (11.3–15.3)99.6 (99.4–99.7)6.1 (5.7–6.5)0.2 (0.1–0.2)24.7 (20.1–29.3)
Two or more positive DAA*154/39185.6 (79.6–90.3)96.7 (96.3–97.1)39.4 (34.5–44.4)99.6 (99.5–99.8)26.1 (23.4–28.3)0.1 (0.1–0.2)63.1 (54.2–72.0)
Three or more positive DAA*140/26377.8 (71.0–83.6)98.3 (98.0–98.6)53.2 (47.0–59.4)99.4 (99.2–99.6)45.7 (39.0–52.5)0.2 (0.2–0.3)73.5 (64.9–82.1)
Only ICA persistently positive6/3893.3 (1.2–7.1)94.7 (94.2–95.2)1.5 (0.6–3.3)97.5 (97.1–97.9)0.6 (0.3–1.3)1.0 (1.0–1.0)2.9 (0.5–5.3)
Persistent double positivity*37/8220.6 (14.9–27.2)99.4 (99.2–99.5)45.1 (34.1–56.5)98.0 (97.7–98.4)33.0 (22.0–49.4)0.8 (0.8–0.8)76.4 (59.5–93.3)
pICA, pIAA11/126.1 (3.1–10.7)100 (99.9–100)91.7 (61.5–99.8)97.7 (97.3–98.0)441.8 (74.2–2659.9)0.9 (0.9–1.0)100 (100–100)
pICA, pGADA2/261.1 (0.1–4.0)99.7 (99.5–99.8)7.7 (0.9–25.1)97.6 (97.2–97.9)3.3 (0.9–12.6)1.0 (1.0–1.0)11.2 (0.0–25.8)
pICA, pIA-2A24/4413.3 (8.7–19.2)99.7 (99.6–99.8)54.5 (38.8–69.9)97.9 (97.5–98.2)48.2 (27.3–85.0)0.9 (0.8–0.9)77.7 (60.3–95.0)
Persistent triple positivity*53/12129.4 (22.9–36.7)99.1 (98.8–99.3)43.8 (34.8–53.1)98.3 (97.9–98.5)31.3 (22.6–43.0)0.7 (0.7–0.8)64.8 (49.5–80.1)
pICA, pIAA, pGADA10/185.6 (2.7–10.0)99.9 (99.8–100)55.6 (30.8–78.5)97.7 (97.3–98.0)50.2 (20.6–122.3)0.9 (0.9–1.0)72.8 (47.4–98.2)
pICA, pIAA, pIA-2A20/2811.1 (6.9–16.6)99.9 (99.8–100)71.4 (51.3–86.8)97.8 (97.5–98.2)100.4 (45.9–221.2)0.9 (0.9–0.9)87.0 (66.9–100)
pICA, pGADA, pIA-2A23/7512.8 (8.3–18.6)99.3 (99.1–99.5)30.7 (20.5–42.4)97.9 (97.5–98.2)17.8 (11.1–28.1)0.9 (0.8–0.9)52.6 (32.6–72.5)
All four DAA persistently positive55/8030.6 (23.9–37.8)99.7 (99.5–99.8)68.8 (57.4–78.7)98.3 (98.0–98.6)88.4 (57.0–137.6)0.7 (0.7–0.7)83.4 (71.7–95.0)
Persistently positive for at least ICA151/67283.9 (77.7–88.9)92.8 (92.2–93.4)22.5 (19.4–25.8)99.6 (99.4–99.7)11.6 (10.6–12.5)0.2 (0.1–0.2)41.2 (34.1–48.3)
≥2 DAA persistently positive*145/28380.6 (74.0–86.1)98.1 (97.7–98.4)51.2 (45.3–57.2)99.5 (99.3–99.7)42.2 (36.5–47.7)0.2 (0.1–0.3)73.2 (64.5–81.8)
≥3 DAA persistently positive*108/20160.0 (52.4–67.2)98.7 (98.4–99.0)53.7 (46.6–60.8)99.0 (98.7–99.2)46.6 (37.5–57.3)0.4 (0.3–0.5)73.0 (63.0–83.0)
  • Data are % (95% CI) unless otherwise indicated. Type 1 diabetes/all progressors/all subjects positive for the given specificity; p, persistently positive autoantibody. In the case of defined autoantibody categories, each individual is included in only one category.

  • *ICA positivity-based categorization. The data in bold represent the highest or lowest (−LR) value for each characteristic.