Table 2.
Meta-analyzed associations of N-glycan traits with medication use in the full models
| N (users/non-users) | Metformin | Statin | ACE inhibitor/ARB | Type 2 diabetes vs controls | |||||
| 1740 | 1070 | 1918 | 804 | 1268 | 1434 | ||||
| Glycan trait | Description | Beta | P value | Beta | P value | Beta | P value | Beta | P value |
| Complexity | |||||||||
| CA2 | Relative abundance of A2 within complex-type glycans | −0.2314 | 5.24E-08 | −0.1126 | 5.67E-02 | −0.1206 | 3.38E-02 | −0.1594 | 6.09E-03 |
| CA3 | Relative abundance of A3 within complex-type glycans | 0.2504 | 1.93E-09 | 0.1205 | 1.01E-01 | 0.1105 | 5.71E-02 | 0.1856 | 1.39E-03 |
| MHy | Ratio of high mannose-to-hybrid glycans | 0.0434 | 3.60E-01 | 0.1705 | 3.76E-04 | 0.0630 | 7.11E-01 | −0.1496 | 2.13E-01 |
| Fucosylation (F) | |||||||||
| A2F | In A2 | −0.2568 | 3.40E-09 | −0.2447 | 2.36E-07 | −0.1717 | 6.83E-02 | −0.2248 | 5.63E-05 |
| A2EF | In A2 with α2.6-sialylation | −0.2205 | 9.97E-07 | −0.2611 | 5.45E-08 | −0.1720 | 1.22E-02 | −0.0435 | 6.82E-01 |
| A2E0F | In A2 without α2.6-sialylation | −0.2044 | 7.26E-06 | −0.1340 | 8.28E-03 | −0.1065 | 6.81E-02 | −0.2654 | 3.73E-06 |
| A2LF | In A2 with α2.3-sialylation | −0.2370 | 1.98E-08 | −0.2719 | 6.92E-09 | −0.1202 | 1.30E-01 | 0.10146 | 2.83E-01 |
| A2L0F | In A2 without α2.3-sialylation | −0.2411 | 4.38E-08 | −0.2252 | 1.87E-06 | −0.1603 | 6.81E-02 | −0.2370 | 1.94E-05 |
| A2S0F | In A2 without sialylation | −0.1378 | 1.53E-01 | −0.0461 | 4.38E-01 | −0.0779 | 1.82E-01 | 0.1458 | 1.01E-02 |
| A3EF | In A3 with α2.6-sialylation | −0.1712 | 1.88E-04 | −0.2524 | 3.69E-08 | −0.0919 | 8.09E-02 | −0.0936 | 1.17E-01 |
| A3LF | In A3 with α2.3-sialylation | −0.1737 | 1.53E-04 | −0.2449 | 5.89E-08 | −0.0798 | 1.41E-01 | −0.0394 | 5.37E-01 |
| A3L0F | In A3 without α2.3-sialylation | −0.2183 | 9.52E-04 | −0.3259 | 3.85E-06 | −0.1621 | 1.50E-03 | −0.1980 | 2.05E-03 |
| A4F | In A4 | −0.1768 | 9.97E-05 | −0.2198 | 1.17E-06 | −0.0153 | 7.31E-02 | −0.0686 | 2.66E-01 |
| Galactosylation (G) | |||||||||
| A2FG | Per antenna within fucosylated A2 | 0.1080 | 9.93E-02 | −0.0191 | 9.34E-01 | −0.0191 | 9.34E-01 | 0.2780 | 8.22E-07 |
| A2F0G | Per antenna in non-fucosylated A2 | 0.2062 | 1.10E-02 | 0.1359 | 8.28E-03 | 0.1125 | 5.04E-01 | 0.2651 | 4.93E-06 |
| A2FS0G | Per antenna within fucosylated non-sialylated A2 | 0.0260 | 9.79E-01 | −0.0132 | 9.34E-01 | −0.0132 | 9.34E-01 | −0.1549 | 1.43E-02 |
| A2SG | Per antenna in sialylated A2 | 0.2648 | 8.79E-10 | 0.1925 | 7.14E-05 | 0.1259 | 8.09E-02 | 0.2650 | 5.97E-07 |
| Bisection (B) | |||||||||
| A2FSB | In fucosylated sialylated A2 | −0.1482 | 4.29E-03 | −0.1376 | 1.15E-02 | −0.0700 | 2.08E-01 | −0.1341 | 2.68E-01 |
| A2FS0B | In fucosylated non-sialylated A2 | 0.2694 | 3.54E-11 | 0.1214 | 1.09E-02 | 0.0116 | 9.17E-01 | 0.4347 | 1.98E-12 |
| A2F0S0B | In non-fucosylated non-sialylated A2 | −0.0306 | 9.79E-01 | −0.0385 | 9.34E-01 | −0.0385 | 9.34E-01 | 0.1478 | 1.11E-02 |
| Sialylation (S) | |||||||||
| A2GS | Per galactose within A2 | 0.2032 | 9.61E-02 | 0.1173 | 2.06E-02 | 0.1063 | 2.98E-01 | 0.4359 | 6.40E-04 |
| A2FGS | Per galactose within fucosylated A2 | 0.1608 | 3.28E-01 | 0.0050 | 9.49E-01 | 0.0254 | 8.97E-01 | 0.5749 | 2.65E-08 |
| A3S | Per antenna within A4 | 0.0867 | 3.93E-01 | −0.0103 | 9.34E-01 | 0.0444 | 5.04E-01 | 0.1545 | 6.09E-03 |
| A4S | In A4 | −0.1214 | 4.72E-02 | −0.0515 | 3.59E-01 | −0.0692 | 2.08E-01 | −0.2984 | 2.08E-07 |
| A4FGS | Per galactose within fucosylated A4 | −0.0996 | 1.99E-01 | −0.0781 | 1.23E-01 | −0.0756 | 1.82E-01 | −0.2186 | 1.03E-04 |
| α2.6-sialylation (E) | |||||||||
| A2E | Per antenna within A2 | 0.2128 | 4.48E-05 | 0.1122 | 2.51E-02 | 0.1240 | 2.08E-01 | 0.4888 | 3.03E-04 |
| A2FGE | Per galactose within fucosylated A2 | 0.1060 | 6.29E-01 | −0.0292 | 8.43E-01 | −0.0069 | 9.54E-01 | 0.5371 | 1.98E-03 |
| A3E | Per antenna within A3 | −0.0291 | 9.79E-01 | −0.0959 | 4.73E-02 | 0.0653 | 2.08E-01 | 0.4274 | 1.71E-11 |
| A4E | Per antenna in A4 | −0.1324 | 1.47E-02 | −0.0187 | 9.34E-01 | −0.0153 | 9.22E-01 | 0.3450 | 8.76E-09 |
| A4FGE | Per galactose within fucosylated A4 | −0.0987 | 1.99E-01 | −0.1249 | 1.19E-02 | −0.0047 | 9.54E-01 | 0.4231 | 9.36E-02 |
| A4F0GE | Per galactose in non-fucosylated A4 | −0.1560 | 1.57E-03 | 0.0050 | 9.70E-01 | −0.0318 | 7.74E-01 | 0.2734 | 3.73E-06 |
| α2.3-sialylation (L) | |||||||||
| A4FGL | Per galactose within fucosylated A4 | 0.0234 | 9.79E-01 | 0.0541 | 3.52E-01 | −0.0271 | 8.63E-01 | −0.4009 | 2.11E-03 |
| A4F0GL | Per galactose within non-fucosylated A4 | 0.1086 | 9.93E-02 | 0.0075 | 9.49E-01 | 0.0125 | 9.17E-01 | −0.3826 | 2.06E-10 |
| A2F0GL | Per galactose within fucosylated A2 | 0.1100 | 9.93E-02 | 0.1205 | 1.48E-02 | 0.0044 | 9.54E-01 | −0.2108 | 1.18E-04 |
| A3L | Per antenna within A3 | 0.0884 | 3.15E-01 | 0.0575 | 2.80E-01 | −0.0088 | 9.41E-01 | −0.4902 | 5.73E-14 |
| A4L | Per antenna within A4 | 0.0496 | 9.79E-01 | −0.0149 | 9.34E-01 | −0.0216 | 8.97E-01 | −0.4467 | 3.50E-13 |
| IgG-related | |||||||||
| TA2FS0 | Fucosylated non-sialylated A2 in total | −0.2497 | 7.91E-09 | −0.1471 | 3.19E-03 | −0.1235 | 9.95E-02 | −0.0378 | 3.50E-13 |
Regression coefficient (beta) and adjusted p values are shown per association. Blue: negative associations, red: positive associations, green: adjusted p values significant after correction according to the Benjamini-Hochberg procedure for multiple comparison. The full models always contain age, sex, the interaction thereof, BMI, HDL, non-HDL, CVD, duration of diabetes and eGFR; for metformin, SU derivatives and insulin, additional adjustment for HbA1c, for ACE inhibitors/ARB additional adjustment for diabetic nephropathy and MAP and for statins additional adjustment for smoking (ever and current) was performed. In the two outmost right columns, ‘type 2 diabetes vs controls’, the meta-analyzed associations of these glycan traits with type 2 diabetes are shown, according to model 3 from Dotz et al19 which was adjusted for the covariates age, sex, the interaction thereof, BMI, HDL, non-HDL and smoking.
ARB, angiotensin II receptor blocker; BMI, body mass index; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; MAP, mean arterial pressure; MHy, mannose-to-hybrid glycans; SU, sulfonylurea.