Table 2.
Key Outcomes Related to Safety and Efficacy
| Measurement | Placebo | Betaine | Placebo | Betaine | Difference in Change | P Value |
|---|---|---|---|---|---|---|
| Baseline, Mean ± SE | Baseline, Mean ± SE | Mean Change From Baseline (95% CI) | Mean Change From Baseline (95% CI) | |||
| Vital signs | ||||||
| Weight, kg | 97.0 ± 4.7 | 91.0 ± 4.5 | 0.6 (−0.4 to 1.6) | 0.3 (–0.7 to 1.3) | −0.3 (–1.7 to 1.1) | 0.639 |
| BMI, kg/m2 | 32.1 ± 1.0 | 31.0 ± 1.0 | 0.2 (–0.1 to 0.6) | 0.1 (–0.2 to 0.5) | −0.1 (–0.5 to 0.4) | 0.790 |
| Waist, cm | 111.8 ± 3.1 | 105.0 ± 3.0 | 0.9 (–1.1 to 2.9) | 1.5 (–0.4 to 3.5) | 0.6 (–2.1 to 3.4) | 0.633 |
| SBP, mm Hg | 132 ± 4 | 132 ± 3 | 0.8 (–8.4 to 10.0) | 4.0 (–5.1 to 13.1) | 3.2 (–9.7 to 16.2) | 0.612 |
| DBP, mm Hg | 79 ± 3 | 80 ± 3 | 0.1 (–4.4 to 4.5) | 0.5 (–4.0 to 5.0) | 0.4 (–6.0 to 6.6) | 0.901 |
| Endocrine | ||||||
| HbA1C, %a | 6.1 ± 0.1 | 6.1 ± 0.1 | 0.1 (–0.1 to 0.3) | 0.1 (–0.1 to 0.3) | 0.0 (–0.2 to 0.3) | 0.925 |
| Fasting glucose, mg/dL | 107 ± 5 | 111 ± 5 | 3 (–4 to 9) | −5 (–12 to 1) | −8 (–17 to 1) | 0.080 |
| 2-Hour glucose, mg/dL | 187 ± 17 | 180 ± 17 | −4 (–22 to 13) | 7 (–10 to 25) | 12 (–12 to 36) | 0.324 |
| AUC glucose | 21,662 ± 1402 | 22,263 ± 1351 | −413 (–1749 to 923) | 340 (–993 to 1672) | 752 (–1134 to 2640) | 0.419 |
| Fasting insulin, μU/mL | 18 ± 2 | 16 ± 2 | −2 (–5 to 1) | −2 (–5 to 1) | 0 (–5 to 5) | 0.994 |
| 2-Hour insulin, μU/mL | 109 ± 18 | 123 ± 18 | 10 (–19 to 38) | −17 (–45 to 12) | −26 (–67 to 14) | 0.193 |
| AUC insulin | 10,281 ± 1360 | 10,116 ± 1310 | 427 (–887 to 1740) | −1553 (–2866 to –240) | −1980 (–3837 to –123) | 0.038b |
| C-peptide, ng/mL | 3.8 ± 0.3 | 3.3 ± 0.3 | −0.2 (–0.6 to 0.3) | −0.2 (–0.7 to 0.3) | −0.0 (–0.7 to 0.6) | 0.906 |
| AUC C-peptide | 1208 ± 88 | 1118 ± 85 | −56 (–127 to 15) | −69 (–142 to 5) | −12 (–115 to 90) | 0.808 |
| TSH, μU/mL | 2.4 ± 0.3 | 1.7 ± 0.3 | −0.4 (–0.8 to 0.1) | −0.1 (–0.6 to 0.3) | 0.2 (–0.4 to 0.9) | 0.438 |
| Cortisol, μg/dL | 10.5 ± 1.5 | 11.6 ± 1.4 | −2.0 (–5.1 to 1.1) | −3.0 (–6.0 to 0.0) | 1.0 (–5.3 to 3.3) | 0.640 |
| IGF-1, ng/mL | 101 ± 13 | 114 ± 12 | −8.2 (–16 to –0.3) | −4.7 (–12.5 to 3.0) | 3.4 (–7.6 to 14.5) | 0.528 |
| Calcium, mg/dL | 9.2 ± 0.1 | 9.1 ± 0.2 | −0.2 (–0.3 to –0.0) | −0.2 (–0.3 to 0.0) | 0.0 (–0.2 to 0.2) | 0.775 |
| Lipids, mg/dL | ||||||
| Total cholesterol | 165 ± 9 | 168 ± 8 | −7 (–20 to 7) | 15 (1 to 28) | 21 (3 to 40) | 0.032b |
| HDL cholesterolc | 50 ± 3 | 44 ± 3 | −1 (–4 to 2) | −1 (–4 to 2) | 0 (–4 to 4) | 0.845 |
| LDL cholesterolc | 130 ± 9 | 111 ± 9 | −7 (–16 to 2) | 2 (–6 to 11) | 9 (–3 to 22) | 0.106 |
| Triglycerides | 131 ± 19 | 141 ± 19 | −13 (–57 to 31) | 54 (11 to 97) | 67 (5 to 129) | 0.069 |
| Renal | ||||||
| Creatinine, mg/dL | 0.8 ± 0.0 | 0.8 ± 0.0 | 0.0 (–0.0 to 0.1) | −0.1 (–0.1 to –0.0) | −0.1 (–0.2 to –0.0) | 0.030b |
| eGFR, mL/min per 1.73 m2 | 93 ± 4 | 97 ± 4 | −0.2 (–4 to 3) | 3 (–1 to 7) | 3 (–2 to 8) | 0.365 |
| Uric acid | 6 ± 0.3 | 6 ± 0.3 | 0.1 (–0.4 to 0.5) | −0.2 (–0.6 to 0.2) | −0.3 (–1 to 0.3) | 0.543 |
| BUN, mg/dL | 14 ± 1 | 16 ± 1 | 2 (–1 to 4) | 0 (–3 to 2) | −2 (–6 to 2) | 0.198 |
| BUN–creatinine ratio, mL/min per 1.73 m2 | 17.5 ± 1.7 | 19.4 ± 1.6 | 1.4 (–1.7 to 4.5) | 1.5 (–1.6 to 4.5) | 0.1 (–4.3 to 4.5) | 0.414 |
| Sodium, mmol/L | 141 ± 0.5 | 141.1 ± 0.5 | 0.2 (–1.5 to 1.6) | 0.2 (–1.2 to 1.5) | 0.0 (–2.0 to 2.0) | 0.999 |
| Potassium, mmol/L | 4.3 ± 0.1 | 4.3 ± 0.1 | 0.0 (–0.2 to 0.1) | 0.1 (–0.1 to 0.2) | 0.1 (–0.1 to 0.3) | 0.146 |
| Chloride, mmol/L | 102 ± 0.6 | 102 ± 0.6 | 0.6 (–0.8 to 2.1) | −0.3 (–1.7 to 1.2) | −0.9 (–2.9 to 1.2) | 0.384 |
| Hepatic | ||||||
| ALT, IU/L | 22 ± 3 | 27 ± 3 | −1.4 (–5.8 to 3.1) | 0.7 (–3.7 to 5.1) | 2.1 (–4.2 to 8.4) | 0.534 |
| AST, IU/L | 23 ± 2 | 23 ± 2 | −0.6 (–3.8 to 2.6) | 1.0 (–2.2 to 4.2) | 1.6 (–2.9 to 6.1) | 0.253 |
| GGT, IU/L | 31 ± 11 | 44 ± 10 | −1 (–21 to 19) | 11 (–9 to 30) | 11 (–39 to 17) | 0.649 |
| ALP, IU/L | 68 ± 4 | 60 ± 4 | −1 (–5to 2) | −9 (–13 to –6) | −8 (–13 to –3) | 0.005d |
| FGF-21, pg/mL | 456 ± 73 | 317 ± 70 | −56 (–135 to 23) | −34 (–113 to 45) | 22 (–90 to 134) | 0.683 |
| CK-18, U/L | 181 ± 18 | 163 ± 17 | 12 (–14 to 38) | 23 (–2 to 49) | 11 (–25 to 48) | 0.519 |
| Other | ||||||
| hsCRP, mg/L | 3.3 ± 1.0 | 1.5 ± 1.0 | 0.1 (–1.2 to 1.5) | −0.1 (–1.4 to 1.3) | −0.2 (–2.1 to 1.7) | 0.828 |
| Hematocrit, % | 40.1 ± 0.9 | 41.2 ± 0.8 | −1.0 (–2.0 to 0.0) | −0.9 (–1.9 to 0.1) | 0.1 (–1.3 to 1.5) | 0.378 |
| Leukocyte count, × 109 cells/L | 6.2 ± 0.3 | 5.9 ± 0.3 | −0.1 (–0.7 to 0.4) | −0.2 (–0.8 to 0.4) | −0.1 (–0.8 to 0.7) | 0.632 |
| Vitamin B12, pg/mL | 547 ± 71 | 564 ± 68 | −16 (–93 to 61) | 77 (–0 to 154) | 93 (–16 to 202) | 0.092 |
| Folate, mg/mL | 16 ± 1 | 17 ± 1 | 0.6 (–0.4 to 1.5) | −0.6 (–1.6 to 0.3) | −1.2 (–2.6 to 0.2) | 0.083 |
| FGF-19, pg/mL | 141 ± 29 | 140 ± 28 | 0.1 (–83 to 83) | 2.9 (–78 to 84) | 2.8 (–114 to 119) | 0.960 |
Outcome measures at baseline and after 12 wk of treatment with betaine or placebo are reported.
Abbreviations: ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; AUC, area under curve; BMI, body mass index; BUN, blood urea nitrogen; CK-18, cytokeratin 18; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; GGT, γ-glutamyl transferase; HDL, high-density lipoprotein; hsCRP, high-sensitive C-reactive protein; LDL, low-density lipoprotein; SBP, systolic blood pressure.
a
Calculation of HbA1C, per NGSP (%) = [0.09148 × IFCC (mmol/mol)] + 2.152).
b
P < 0.05.
c
HDL and LDL conversion calculation: mg/dL × 0.0259 = mmol/L.
d
P < 0.01.