Table 2.
Associations between each risk factor and bone turnover markers and sclerostin among Epidemiology of Diabetes Interventions and Complications participants
| PINP, pg/mL | Bone ALP, U/L | sCTX, pg/mL | TRACP5b, U/L | Sclerostin, pg/mL | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Individual risk factor | Estimate (95% CI) | P-value | Estimate (95% CI) | P-value | Estimate (95% CI) | P-value | Estimate (95% CI) | P-value | Estimate (95% CI) | P-value |
| Current HbA1c, % | −3.5 (−6.3, −0.8) | 0.011 | −0.04 (−0.72, 0.65) | 0.914 | −12.5 (−31.0, 6.0) | 0.186 | −0.07 (−0.21, 0.07) | 0.342 | −3.2 (−10.6, 4.2) | 0.399 |
| Time-weighted mean HbA1c | −0.6 (−4.0, 2.9) | 0.741 | 0.7 (−0.2, 1.5) | 0.109 | 7.2 (−16.1, 30.4) | 0.543 | 0.08 (−0.09, 0.26) | 0.347 | 3.8 (−5.4, 13.1) | 0.415 |
| Any sustained AER ≥ 30, yes vs no | 1.2 (−5.4, 7.8) | 0.721 | 0.4 (−1.3, 2.0) | 0.653 | 34.4 (−9.9, 78.7) | 0.127 | 0.09 (−0.24, 0.43) | 0.584 | 2.8 (−14.9, 20.6) | 0.753 |
| Any AER ≥ 300, yes vs no | 8.5 (−0.3, 17.4) | 0.059 | 1.4 (−0.8, 3.6) | 0.222 | 86.0 (27.1, 144.9) | 0.004 | 0.36 (−0.08, 0.81) | 0.111 | −7.6 (−31.5, 16.3) | 0.532 |
| eGFR, per −20 mL/min/1.73 m2 | 7.6 (4.6, 10.6) | <0.0001 | 1.2 (0.4, 2.0) | 0.002 | 58.4 (38.3, 78.5) | <0.0001 | 0.3 (0.14, 0.46) | <0.0001 | −3.5 (−12, 5.1) | 0.426 |
| Any sustained eGFR < 60 or ESRD (reduced eGFR), yes vs no | 18.2 (7.9,28.4) | <0.0001 | 3.7 (1.2, 6.3) | 0.005 | 176.8 (109.3, 244.4) | <0.0001 | 0.88 (0.36, 1.41) | 0.001 | 0.2 (−28.2, 28.7) | 0.987 |
| Cardiac autonomic neuropathy,a yes vs no | 5.2 (−1.3, 11.8) | 0.117 | 1.2 (−0.4, 2.8) | 0.150 | 29.3 (−14.2, 72.9) | 0.186 | 0.36 (0.03, 0.68) | 0.032 | 6.6 (−10.7, 24.0) | 0.452 |
| Diabetic peripheral neuropathy,b yes vs no | −0.6 (−7.3, 6.2) | 0.866 | 0.3 (−1.4, 1.9) | 0.754 | 12.1 (−32.9, 57.0) | 0.598 | 0.44 (0.10, 0.78) | 0.011 | 13.2 (−5.2, 31.6) | 0.158 |
| AGEc (SIF), every 5 units | 4.3 (0.6, 7.9) | 0.022 | 1.0 (0.1, 1.9) | 0.034 | 28.6 (3.8, 53.4) | 0.024 | 0.24 (0.05, 0.42) | 0.012 | 5.8 (−4.0, 15.5) | 0.244 |
| Sclerostin, pg/mL | −0.03 (−0.08, 0.02) | 0.209 | −0.013 (−0.025, −0.001) | 0.034 | −0.4 (−0.7, −0.1) | 0.014 | −0.001 (−0.004, 0.001) | 0.328 | ||
| IGF-1, ng/mL, per 1 SD | 1.0 (−2.2, 4.1) | 0.546 | −0.2 (−0.9, 0.6) | 0.690 | 22.6 (1.5, 43.7) | 0.036 | −0.07 (−0.23, 0.09) | 0.408 | −3.1 (−11.6, 5.4) | 0.470 |
| IGFBP-1/1000, ng/mL, per 1 SD | −0.3 (−3.5, 2.8) | 0.828 | −0.2 (−1.0, 0.5) | 0.535 | 10.4 (−10.8, 31.5) | 0.336 | 0.15 (−0.01, 0.31) | 0.061 | 2.8 (−5.6, 11.3) | 0.512 |
| IGFBP-3, ng/mL, per 1 SD | −0.5 (−3.7, 2.7) | 0.763 | −0.2 (−1.0, 0.6) | 0.609 | 32.1 (11.0, 53.2) | 0.003 | 0.05 (−0.11, 0.21) | 0.538 | −9.2 (−17.7, −0.7) | 0.034 |
| 25-hydroxyvitamin D, ng/mL | 0.03 (−0.2, 0.26) | 0.772 | 0.001 (−0.056, 0.058) | 0.978 | 0.6 (−0.9, 2.2) | 0.435 | 0.002 (−0.009, 0.014) | 0.705 | −0.3 (−0.9, 0.3) | 0.357 |
| Parathyroid hormone intact, pg/mL | 0.20 (0.02, 0.38) | 0.033 | 0.09 (0.04, 0.13) | <0.0001 | 2.2 (0.9, 3.4) | <0.0001 | 0.004 (−0.006, 0.013) | 0.429 | −0.4 (−0.9, 0.1) | 0.097 |
Models were adjusted for age, sex, and menopause. Bolded values are P < 0.05.
Abbreviations: AER, albumin excretion rate; AGE, advanced glycation end product; bone ALP, bone-specific alkaline phosphatase; EDIC, Epidemiology of Diabetes Interventions and Complications study; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; HbA1c, hemoglobin A1c; IGF-1, insulin-like growth factor 1; IGFBP-1, insulin-like growth factor binding protein 1; IGFBP-3, insulin-like growth factor binding protein 3; PINP, procollagen 1 intact N-terminal propeptide; sCTX, serum C-telopeptide; SIF, skin intrinsic fluorescence; TRACP5b, tartrate-resistant acid phosphatase 5b.
aEDIC year 16-17 (2009-2010).
bEDIC year 13-14 (2006-2007).
cSkin-intrinsic fluorescence: EDIC year 16-17 (2009-2010).