Table 3.
Effect of medication interventions in adults on select metabolic characteristics from the hyperglycemic clamps and OGTTs
| G/M | L+M | MET | PLAC | P for comparisons between treatments at 12 months | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline (n = 67) | 12 months (n = 63) | 15 months (n = 64) | Baseline (n = 68) | 12 months (n = 54) | 15 months (n = 53) | Baseline (n = 65) | 12 months (n = 54) | 15 months (n = 55) | Baseline (n = 62) | 12 months (n = 54) | 15 months (n = 49) | ||
| Anthropometric parameters | |||||||||||||
| Weight (kg) | 104.4 ± 20.0 | 101.4 ± 20.7@ | 103.4 ± 21.5*# | 104.2 ± 21.0 | 97.4 ± 20.7@ | 101.2 ± 20.7*# | 98.1 ± 18.6 | 96.0 ± 19.4@ | 96.7 ± 19.9*# | 101.3 ± 19.6 | 99.2 ± 19.6 | 98.3 ± 20.3 | |
| BMI (kg/m2) | 35.0 ± 5.9 | 34.0 ± 6.1@ | 34.5 ± 6.2*# | 35.6 ± 5.8 | 33.6 ± 5.9@ | 34.9 ± 5.9*# | 35.0 ± 5.1 | 33.9 ± 5.7@ | 34.3 ± 5.8*# | 34.4 ± 6.1 | 33.9 ± 6.1 | 33.4 ± 5.8 | |
| Hyperglycemic clamp parameters | |||||||||||||
| Fasting glucose (mmol/L) | 6.08 ± 0.54 | 5.96 ± 0.55 | 6.31 ± 1.08# | 6.02 ± 0.54 | 5.44 ± 0.53@ | 6.06 ± 0.55# | 6.14 ± 0.60 | 5.92 ± 0.79@ | 6.30 ± 1.09# | 6.11 ± 0.55 | 6.16 ± 0.73 | 6.33 ± 0.82*# | 1, 5 |
| Fasting glucagon (pmol/L) | 9.80 ± 5.15 | 9.31 ± 5.13 | 9.63 ± 4.45 | 8.82 ± 5.11 | 7.12 ± 4.80@ | 7.13 ± 4.38* | 7.66 ± 3.51 | 7.67 ± 4.82 | 8.00 ± 4.19 | 7.68 ± 3.82 | 8.58 ± 5.12 | 8.47 ± 4.56 | |
| Fasting C-peptide (nmol/L) | 1.16 (0.55, 2.43) | 1.05 (0.47, 2.35)@ | 1.12 (0.52, 2.41) | 1.18 (0.63, 2.24) | 1.03 (0.50, 2.13)@ | 1.06 (0.50, 2.23)* | 1.13 (0.57, 2.27) | 1.02 (0.45, 2.28)@ | 1.08 (0.50, 2.34)# | 1.07 (0.50, 2.31) | 1.00 (0.49, 2.06) | 1.04 (0.52, 2.05) | |
| Fasting insulin (pmol/L) | 109.2 (40.2, 296.8) | 91.7 (27.7, 303.7)@ | 103.0 (26.6, 398.2) | 109.9 (41.9, 287.9) | 85.6 (27.6, 265.1)@ | 90.2 (30.3, 268.0)* | 102.9 (36.8, 287.8) | 86.7 (26.5, 284.1)@ | 94.1 (29.6, 299.5)# | 90.1 (28.2, 288.3) | 82.7 (28.3, 241.4) | 90.6 (30.5, 269.4)* | |
| Steady-state glucose (mmol/L) | 11.9 ± 0.7 | 11.8 ± 0.7 | 11.8 ± 0.8 | 11.9 ± 0.6 | 11.7 ± 0.6 | 11.7 ± 0.7 | 11.9 ± 0.6 | 11.8 ± 0.7 | 11.8 ± 0.7 | 11.9 ± 0.5 | 11.8 ± 0.7 | 11.8 ± 0.6 | |
| Steady-state glucagon (pmol/L) | 2.88 ± 2.41 | 2.94 ± 2.88 | 3.14 ± 2.41 | 2.56 ± 1.89 | 1.11 ± 0.94@ | 2.00 ± 1.58*# | 2.26 ± 1.65 | 1.75 ± 1.40@ | 2.49 ± 1.99# | 2.43 ± 1.82 | 2.91 ± 2.94 | 3.15 ± 3.16# | 1, 2, 4, 5 |
| Steady-state C-peptide (nmol/L) | 4.01 (1.91, 8.42) | 3.85 (1.85, 8.02) | 3.58 (1.54, 8.33)*# | 4.06 (2.09, 7.89) | 7.04 (3.09, 16.08)@ | 3.73 (1.87, 7.44)*# | 3.86 (1.98, 7.55) | 3.86 (1.87, 8.00) | 3.65 (1.94, 6.87)* | 3.80 (1.82, 7.95) | 3.56 (1.67, 7.59)@ | 3.49 (1.68, 7.24)* | 4, 5 |
| AGR (pmol/L) | 17.1 ± 8.3 | 16.7 ± 8.9 | 16.6 ± 7.7 | 17.0 ± 9.7 | 12.2 ± 6.0@ | 13.7 ± 7.1*# | 16.0 ± 8.4 | 15.0 ± 7.3 | 16.3 ± 8.3 | 16.2 ± 8.5 | 16.0 ± 8.7 | 16.0 ± 9.7 | |
| ACPRmax (nmol/L) | 4.78 (1.83, 12.52) | 4.68 (1.91, 11.44) | 4.32 (1.58, 11.80)* | 4.93 (2.27, 10.73) | 3.38 (1.18, 9.67)@ | 4.58 (2.21, 9.48)# | 4.83 (1.98, 11.74) | 4.48 (1.94, 10.37) | 4.61 (2.00, 10.66) | 4.90 (2.01, 11.97) | 4.46 (1.67, 11.93)@ | 4.42 (1.54, 12.69)* | 4 |
| M/I (×10−5 mmol/kg/min per pmol/L) | 2.81 (0.65, 12.14) | 3.07 (0.61, 15.52) | 3.38 (0.61, 18.84) | 2.92 (0.75, 11.31) | 2.33 (0.52, 10.50)@ | 3.49 (0.90, 13.54)*# | 3.26 (0.81, 13.07) | 3.89 (0.86, 17.64)@ | 3.53 (0.67, 18.49) | 3.38 (0.68, 16.69) | 3.79 (0.89, 16.05) | 3.93 (1.13, 13.60) | 4, 5 |
| OGTT parameters | |||||||||||||
| Fasting glucose (mmol/L) | 6.22 ± 0.74 | 5.96 ± 0.57@ | 6.32 ± 0.68# | 6.11 ± 0.50 | 5.44 ± 0.59@ | 5.98 ± 0.47*# | 6.21 ± 0.67 | 5.95 ± 0.68@ | 6.35 ± 0.96# | 6.10 ± 0.57 | 6.31 ± 0.69 | 6.29 ± 0.90 | 3, 4, 5, 6 |
| Fasting glucagon (pmol/L) | 9.77 ± 6.01 | 8.85 ± 4.24 | 9.24 ± 4.83 | 8.84 ± 4.74 | 7.51 ± 4.69 | 7.55 ± 4.86* | 7.47 ± 3.38 | 7.24 ± 3.81 | 7.75 ± 4.21 | 8.26 ± 4.65 | 7.74 ± 4.87 | 8.14 ± 4.41 | |
| Fasting C-peptide (nmol/L) | 1.339 ± 0.689 | 1.134 ± 0.428@ | 1.235 ± 0.533# | 1.249 ± 0.428 | 1.086 ± 0.416@ | 1.108 ± 0.451* | 1.234 ± 0.416 | 1.116 ± 0.534@ | 1.192 ± 0.577# | 1.133 ± 0.437 | 1.121 ± 0.397 | 1.108 ± 0.412# | |
| iAUC glucose (mmol/L) | 610.5 ± 260.4 | 692.3 ± 238.0 | 622.3 ± 269.1 | 577.4 ± 243.5 | 464.7 ± 202.7@ | 583.1 ± 251.8# | 601.9 ± 248.0 | 638.5 ± 232.1 | 626.7 ± 319.0 | 635.0 ± 237.9 | 602.1 ± 279.1 | 628.5 ± 270.2 | 3, 4, 6 |
| dAUC glucagon (pmol/L) | −848.4 ± 560.8 | −797.0 ± 492.7 | −833.3 ± 507.5 | −860.7 ± 510.4 | −774.5 ± 553.1 | −773.3 ± 573.0 | −697.2 ± 412.5 | −698.8 ± 392.3 | −686.7 ± 481.2 | −751.2 ± 520.0 | −742.9 ± 582.6 | −719.1 ± 534.7 | |
| iAUC C-peptide (nmol/L) | 454.2 ± 174.6 | 437.6 ± 154.5@ | 417.0 ± 165.9* | 439.3 ± 140.9 | 516.6 ± 161.0@ | 438.0 ± 144.8# | 447.1 ± 141.6 | 454.3 ± 145.3 | 406.6 ± 141.9*# | 444.7 ± 146.7 | 422.6 ± 139.1 | 413.0 ± 136.0* | 4, 5 |
Data are means ± SD for normally distributed and geometric means (95% CI) for non–normally distributed data; for the latter, P values from the log-transformed data are presented. Within-treatment comparisons:
@
P < 0.05 12 months vs. baseline;
*
P < 0.05 15 months vs. baseline;
#
P < 0.05 15 months vs. 12 months. Between-treatment comparisons adjusted for weight at baseline and 12 months; if P < 0.05 for comparison across four treatment arms, P < 0.05 for between-treatment comparisons: 1, G/M vs. L+M; 2, G/M vs. MET; 3, G/M vs. PLAC; 4, L+M vs. MET; 5, L+M vs. PLAC; 6, MET vs. PLAC.