Table 1.
Characteristics of the CART-defined groups of islet autoantibody-positive patients in the DiMelli cohort included in the main analysis.
| P1 | P2 | P3 | P4 | P5 | P6 | P7 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Variable | N | median [IQR] or n(%) | n | median [IQR] or n(%) | n | median [IQR] or n(%) | n | median [IQR] or n(%) | n | median [IQR] or n(%) | n | median [IQR] or n(%) | n | median [IQR] or n(%) | p-value |
| Fasting C-peptide [nmol/l] | 47 | 0.13 [0.00;0.20] | 22 | 0.33 [0.21;0.46] | 315 | 0.07 [0.00;0.13] | 212 | 0.13 [0.07;0.17] | 56 | 0.38 [0.26;0.54] | 389 | 0.17 [0.10;0.23] | 47 | 0.30 [0.20;0.40] | <0.001 |
| Sex: Male | 47 | 26 (55.3%) | 22 | 13 (59.1%) | 315 | 158 (50.2%) | 212 | 104 (49.06%) | 56 | 36 (64.3%) | 389 | 235 (60.4%) | 47 | 35 (74.5%) | 0.003 |
| Age [years] | 47 | 5.02 [3.05;6.08] | 22 | 9.13 [8.14;10.18] | 315 | 5.42 [3.26;7.02] | 212 | 9.44 [8.89;10.16] | 56 | 14.09 [12.62;15.95] | 389 | 13.54 [12.07;14.87] | 47 | 13.18 [11.87;15.74] | <0.001 |
| BMI SDSa | 47 | -0.66 [-1.35;0.13] | 22 | -0.49 [-0.79;0.53] | 315 | -0.65 [-1.54;0.13] | 212 | -0.61 [-1.34;0.36] | 56 | 0.01 [-0.54;1.23] | 389 | -0.74 [-1.48;-0.11] | 47 | 1.42 [1.18;1.88] | <0.001 |
| HbA1c [%] | 47 | 7.20 [6.40;7.65] | 22 | 7.10 [6.45;7.60] | 315 | 10.50 [9.30;11.70] | 212 | 11.30 [10.20;12.80] | 56 | 7.30 [6.30;7.93] | 389 | 11.90 [10.50;13.50] | 47 | 10.80 [10.00;12.10] | <0.001 |
| Family History T1D | 47 | 6 (12.8%) | 22 | 3 (13.6%) | 315 | 22 (7.0%) | 212 | 10 (4.7%) | 56 | 7 (12.5%) | 389 | 26 (6.7%) | 47 | 4 (8.5%) | 0.16 |
| Family History T2D | 47 | 0 (0.0%) | 22 | 0 (0.0%) | 315 | 2 (0.6%) | 212 | 3 (1.4%) | 56 | 7 (12.5%) | 389 | 12 (3.7%) | 47 | 1 (2.1%) | 0.001 |
| Other autoimmunityb | 47 | 8 (17.0%) | 22 | 2 (9.1%) | 315 | 50 (15.9%) | 212 | 35 (16.5%) | 56 | 8 (14.3%) | 389 | 75 (19.3%) | 47 | 7 (14.9%) | 0.85 |
| Treatment: Insulin | 47 | 43 (91.5%) | 22 | 19 (86.4%) | 315 | 313 (99.4%) | 212 | 210 (99.1%) | 56 | 50 (89.3%) | 389 | 385 (99.0%) | 47 | 45 (95.7%) | <0.001 |
| Insulin dose [U/day/kg]c | 34 | 0.52 [0.15;0.83] | 14 | 0.46 [0.33;0.63] | 275 | 0.87 [0.63;1.18] | 189 | 0.99 [0.69;1.23] | 45 | 0.46 [0.31;0.64] | 338 | 0.98 [0.75;1.26] | 37 | 0.87 [0.60;1.09] | <0.001 |
| Ketonuria | 40 | 22 (55.0%) | 18 | 12 (66.7%) | 301 | 269 (89.4%) | 202 | 191 (94.5%) | 45 | 31 (68.9%) | 365 | 337 (92.3%) | 45 | 41 (91.1%) | <0.001 |
| Insulin sensitivityd | 27 | 15.82 [14.59;17.07] | 11 | 12.47 [11.51;13.70] | 163 | 10.46 [8.74;12.34] | 128 | 7.99 [6.61;9.45] | 27 | 9.97 [7.14;11.05] | 199 | 6.28 [5.06;7.69] | 24 | 4.71 [3.76;5.38] | <0.001 |
| Triglycerides [mg/dl] | 41 | 64.0 [53.0;81.0] | 19 | 62.0 [55.5;78.5] | 243 | 72.0 [57.5;92.5] | 171 | 75.0 [57.0;99.5] | 45 | 74.0 [57.0;106.0] | 291 | 85.0 [67.0;108.5] | 37 | 120.0 [83.0;157.0] | <0.001 |
| Vitamin D3 [ng/ml] | 42 | 27.6 [18.2;35.0] | 21 | 28.8 [20.6;37.3] | 292 | 27.1 [19.5;36.0] | 198 | 24.8 [15.6;33.2] | 51 | 20.3 [13.0;32.1] | 357 | 24.1 [15.0;32.6] | 45 | 22.2 [14.4;30.0] | 0.005 |
| Vitamin D3 deficiencye | 42 | 24 (57.1%) | 21 | 12 (57.1%) | 292 | 166 (56.8%) | 198 | 126 (63.6%) | 51 | 37 (72.5%) | 357 | 244 (68.3%) | 45 | 34 (75.6%) | 0.02 |
| IFNɣ [pg/ml] | 23 | 10.3 [6.5;21.2] | 15 | 6.3 [4.7;10.2] | 170 | 7.7 [5.0;13.7] | 133 | 5.8 [4.0;10.1] | 24 | 4.6 [3.2;8.7] | 217 | 4.7 [3.5;7.3] | 21 | 4.9 [3.3;6.2] | <0.001 |
| IL-10 [pg/ml] | 23 | 1.0 [0.6;1.4] | 15 | 0.8 [0.5;1.3] | 170 | 1.2 [0.7;2.5] | 133 | 0.7 [0.5;1.2] | 24 | 0.8 [0.5;1.3] | 217 | 0.6 [0.5;1.2] | 21 | 0.6 [0.4;1.0] | <0.001 |
| IL-12p70 [pg/ml] | 23 | 0.3 [0.2;0.6] | 15 | 0.3 [0.2;0.7] | 170 | 0.3 [0.2;0.8] | 133 | 0.3 [0.1;0.6] | 24 | 0.3 [0.1;0.4] | 217 | 0.3 [0.1;0.6] | 21 | 0.3 [0.1;0.5] | 0.10 |
| IL-1beta [pg/ml] | 23 | 1.0 [0.3;2.3] | 15 | 0.3 [0.2;5.1] | 170 | 1.2 [0.5;4.7] | 133 | 0.5 [0.2;2.5] | 24 | 0.6 [0.3;2.6] | 217 | 0.8 [0.3;2.9] | 21 | 0.8 [0.3;2.0] | 0.05 |
| IL-2 [pg/ml] | 23 | 0.3 [0.1;0.9] | 15 | 0.4 [0.1;0.8] | 170 | 0.4 [0.1;1.1] | 133 | 0.2 [0.1;1.0] | 24 | 0.1 [0.0;0.8] | 217 | 0.2 [0.1;0.7] | 21 | 0.2 [0.0;0.5] | 0.14 |
| IL-6 [pg/ml] | 23 | 1.9 [0.7;3.5] | 15 | 1.7 [0.5;9.3] | 170 | 2.3 [0.9;8.8] | 133 | 1.1 [0.6;4.6] | 24 | 1.3 [0.6;8.5] | 217 | 1.3 [0.6;4.8] | 21 | 1.4 [0.7;3.7] | 0.09 |
| IL-8 [pg/ml] | 23 | 70.3 [15.9;1393.3] | 15 | 98.1 [16.8;1973.6] | 170 | 524.5 [95.8;2618.1] | 133 | 147.1 [31.6;1303.9] | 24 | 146.5 [63.7;925.2] | 217 | 242.9 [53.9;1628.9] | 21 | 470.3 [112.5;1235.3] | 0.06 |
| TNF [pg/ml] | 23 | 4.6 [2.9;8.0] | 15 | 3.9 [2.0;6.9] | 170 | 4.3 [2.9;7.9] | 133 | 3.0 [1.9;4.8] | 24 | 3.1 [1.9;5.8] | 217 | 3.0 [1.7;5.4] | 21 | 3.4 [1.8;4.6] | <0.001 |
| HLAf - high risk | 36 | 12 (33.3%) | 18 | 7 (38.9%) | 270 | 89 (33.0%) | 181 | 50 (27.6%) | 45 | 12 (26.7%) | 347 | 99 (28.5%) | 39 | 7 (17.9%) | 0.78 |
| - moderate risk | 36 | 12 (33.3%) | 18 | 4 (22.2%) | 270 | 67 (24.8%) | 181 | 53 (29.3%) | 45 | 9 (20.0%) | 347 | 89 (25.6%) | 39 | 11 (28.2%) | |
| - neutral genotypes | 36 | 9 (25.0%) | 18 | 6 (33.3%) | 270 | 100 (37.0%) | 181 | 65 (35.9%) | 45 | 21 (46.7%) | 347 | 136 (39.2%) | 39 | 20 (51.3%) | |
| - protective genotypes | 36 | 3 (8.3%) | 18 | 1 (5.6%) | 270 | 14 (5.2%) | 181 | 13 (7.2%) | 45 | 3 (6.7%) | 347 | 23 (6.6%) | 39 | 1 (2.6%) | |
| Genetic Risk Scoreg | 34 | 10.93 [10.20;11.57] | 18 | 11.22 [9.97;11.61] | 258 | 10.73 [10.22;11.29] | 178 | 10.80 [10.13;11.20] | 42 | 10.52 [9.96;10.91] | 337 | 10.71 [10.15;11.19] | 35 | 10.76 [10.20;11.42] | 0.331 |
| N autoantibodies - 1 | 47 | 6 (12.8%) | 22 | 4 (18.2%) | 315 | 26 (8.2%) | 212 | 28 (13.2%) | 56 | 7 (12.5%) | 389 | 28 (7.2%) | 47 | 4 (8.5%) | 0.17 |
| - 2 | 47 | 9 (19.1%) | 22 | 4 (18.2%) | 315 | 80 (25.4%) | 212 | 48 (22.6%) | 56 | 12 (21.4%) | 389 | 104 (26.7%) | 47 | 8 (17.0%) | |
| - 3 | 47 | 12 (25.5%) | 22 | 5 (22.7%) | 315 | 106 (33.6%) | 212 | 62 (29.2%) | 56 | 26 (46.4%) | 389 | 133 (34.2%) | 47 | 16 (34.0%) | |
| - 4 | 47 | 20 (42.5%) | 22 | 9 (40.9%) | 315 | 103 (32.7%) | 212 | 74 (34.9%) | 56 | 11 (19.6%) | 389 | 124 (31.9%) | 47 | 19 (40.4%) | |
| IAA positiveh | 44 | 37 (84.1%) | 18 | 12 (66.7%) | 313 | 254 (81.1%) | 209 | 136 (65.1%) | 49 | 36 (73.5%) | 385 | 231 (60.0%) | 45 | 32 (71.1%) | <0.001 |
| GADA positive | 47 | 36 (76.6%) | 22 | 14 (63.6%) | 315 | 201 (63.8%) | 212 | 141 (66.5%) | 56 | 37 (66.1%) | 389 | 290 (74.5%) | 47 | 36 (76.6%) | 0.04 |
| IA-2A positive | 47 | 36 (76.6%) | 22 | 17 (77.3%) | 315 | 237 (75.2%) | 212 | 165 (77.8%) | 56 | 40 (71.4%) | 389 | 311 (79.9%) | 47 | 37 (78.7%) | 0.74 |
| ZnT8A positive | 47 | 31 (66.0%) | 22 | 20 (90.9%) | 315 | 224 (71.1%) | 212 | 164 (77.4%) | 56 | 40 (71.4%) | 389 | 299 (76.9%) | 47 | 39 (83.0%) | 0.09 |
a
SDS: age- and sex-adjusted standard deviation score.
b
Positive for either thyroid peroxidase or tissue transglutaminase autoantibodies.
c
The insulin dose was calculated for insulin-treated patients.
d
Insulin sensitivity score.
e
Defined as <30 ng/ml.
f
High-risk (DR3/4-DQ8 or DR4-DQ8/DR4-DQ8), moderate, neutral, and protective HLA genotypes, as defined by Walter et al.36 (Table S1).
g
Remaining genetic risk score calculated without the HLA-DR/DQ genotype.
h
IAA positive status was only assigned to samples collected <14 days after starting insulin.
IQR, interquartile range; BMI, body mass index; HbA1c, haemoglobin A1c; T1D, type 1 diabetes; T2D, type 2 diabetes; IFNɣ, interferon-ɣ; IL, interleukin; TNF, tumour necrosis factor; HLA, human leukocyte antigen; IAA, insulin autoantibodies; IA-2A, insulinoma-associated antigen-2 autoantibodies; GADA, glutamate decarboxylase (65-kDa isoform) autoantibodies; ZnT8A, zinc transporter-8 autoantibodies.