Table 3.

Energy expenditure and neuroendocrine mediators of energy expenditure in patients with lipodystrophy before and after initiation or withdrawal of metreleptin

	Initiation				Withdrawal			Combined
	Baseline (n = 17)	2 weeks (n = 16)	6 months (n = 15)	P*	Baseline (n = 8)	2 weeks (n = 8)	P	Off (n = 25)	On (n = 24)	P
REE (kcal/24 h)	1805 ± 332	1688 ± 318	1726 ± 309c	0.032w	1565 ± 406	1538 ± 362	0.8	1719 ± 357	1647 ± 346	0.05
24-h EE (kcal/24 h)	2402 ± 383	2272 ± 396	2191 ± 444e	0.0032w,6m	2225 ± 504	2209 ± 467	0.7	2340 ± 412	2256 ± 424	0.03
24-h EE + urinary glucose excretion EE (kcal/24 h)	2424 ± 380	2294 ± 405	2200 ± 446e	0.0022w,6m	2227 ± 504	2214 ± 470	0.8	2357 ± 414	2272 ± 431	0.03
nREE (kcal/24 h)	585 ± 183a	584 ± 251	502 ± 243e	0.6	660 ± 137	670 ± 143g	1	614 ± 172	609 ± 220	0.9
Sleep EE (kcal/24 h)	1858 ± 270a	1758 ± 242	1726 ± 312e	0.0022w,6m	1767 ± 383	1814 ± 307g	0.3	1814 ± 307	1761 ± 288	0.1
TEF (kcal/24 h)	356 ± 132a	350 ± 200	312 ± 192e	0.4	324 ± 179	363 ± 126g	0.3	363 ± 126	342 ± 190	0.4
TEF as % of energy intake	15 ± 5a	14 ± 7a	14 ± 9j	0.9	13 ± 6	16 ± 3	0.3	15 ± 4g	14 ± 7	0.3
AEE (kcal/24 h)	238 ± 178a	234 ± 303a	190 ± 267e	1	335 ± 105	293 ± 133	0.5	256 ± 163g	268 ± 256	0.5
24-h RQ	0.86 ± 0.04	0.86 ± 0.04	0.86 ± 0.03e	1	0.89 ± 0.04	0.86 ± 0.05	0.4	0.86 ± 0.05	0.87 ± 0.04	0.5
10W work efficiency	0.12 (0.10, 0.15)	0.12 (0.09, 0.23)	0.14 (0.11, 0.16) k	0.5	0.11 (0.09,0.13)	0.12 (0.09,0.15)	0.7	0.12 (0.10,0.15)	0.11 (0.09,0.18)	0.6
25W work efficiency	0.20 (0.18, 0.26)	0.22 (0.18, 0.31)	0.24 (0.22, 0.50) k	0.3	0.22 (0.16,0.23)	0.20 (0.17,0.27)	0.6	0.20 (0.18,0.26)	0.22 (0.18,0.27)	0.9
50W work efficiency	0.25 (0.23, 0.28)a	0.27 (0.24, 0.30)	0.27 (0.25,0.42) j	0.1	0.25 (0.22,0.28)	0.26 (0.23,0.35)	0.4	0.26 (0.23,0.29)g	0.27 (0.24,0.29)	0.2
Dopamine (pg/mL)	32 ± 19a	26 ± 6b	24 ± 1m	0.2	24 ± 0	30 ± 10	0.5	31 ± 17g	25 ± 5o	0.06
Epinephrine (pg/mL)	19 ± 1a	19 ± 0b	19 ± 0.4m	0.6	24 ± 15	28 ± 18	0.3	22 ± 11g	21 ± 9o	0.1
Norepinephrine (pg/mL)	262 ± 450a	207 ± 189b	233 ± 124m	0.7	191 ± 70	112 ± 47	0.03	212 ± 371g	201 ± 156o	0.8
Free T3 (pg/mL)	248 (200 270)c	295 (259 315)d	276 (248 300)m	0.0062w, 6m	295 (267 331)	265 (237 323)	0.008	253 (212 281)h	295 (266 320)i	0.0002
TSH (μIU/mL)	2.1 ± 0.8c	2.3 ± 0.7d	1.8 ± 0.9e	0.3	2.1 ± 1.0	2.5 ± 1.4	0.07	2.3 ± 1.0h	2.2 ± 0.8i	0.8
Free T4 (ng/dL)	1.0 ± 0.2c	1.1 ± 0.2d	1.1 ± 0.2e	0.2	1.2 ± 0.2	1.0 ± 0.2	0.002	1.0 ± 0.2h	1.1 ± 0.2i	0.0004
T3 (pg/dL)	91 ± 21c	101 ± 16d	98 ± 14e	0.3	112 ± 26	107 ± 35	0.4	97 ± 28h	105 ± 21i	0.052
Core body temperature (°C)	36.5 ± 0.3	36.5 ± 0.3	36.5 ± 0.3c	0.4	36.6 ± 0.3	36.8 ± 0.4	0.8	36.6 ± 0.4	36.5 ± 0.5	0.4
Weighted skin temperature (°C)	32.5 ± 0.8	32.8 ± 0.5d	33 ± 0.4k	0.7	33.3 ± 0.6m	33.3 ± 0.7	0.8	32.8 ± 0.9i	32.9 ± 0.6p	0.07
Wrist activity (counts/min)	1437 ± 850c	1714 ± 620c	NA	0.3	1204 ± 535m	1205 ± 380m	1	1367 ± 738n	1553 ± 629p	0.3
Hip activity (counts/min)	388 ± 264c	537 ± 370d	NA	0.1	293 ± 137m	269 ± 48m	0.7	352 ± 227n	464 ± 334n	0.1

Data show the mean ± SD for normally distributed metrics and median (interquartile range: 25th, 75th) for nonnormally distributed metrics. Patients in the initiation cohort have data prior to initiation of metreleptin (baseline) and after 2 weeks and 6 months of metreleptin administration. Patients in the withdrawal cohort have data during metreleptin treatment (baseline) and after 2 weeks of metreleptin withdrawal. The combined cohort includes baseline and 2-week data in both groups, categorized by on or off metreleptin status. ^2wP < 0.05 for baseline vs 2 weeks. ^6mP < 0.05 for baseline vs 6 months.

Abbreviations: AEE, activity energy expenditure; EE, energy expenditure; NA, not available; nREE, nonresting energy expenditure (equal to 24-h EE-REE); REE, resting energy expenditure; RQ, respiratory quotient; TEF, thermic effect of feeding.

^a n = 16.

^b n = 15.

^c n = 14.

^d n = 13.

^e n = 12.

^f n = 9.

^g n = 24.

^h n = 22.

ⁱ n = 21.

^j n = 11.

^k n = 10.

^l n = 3.

^m n = 6.

ⁿ n = 20.

^o n = 23.

^p n = 19.

^q Overall P-value for linear mixed-effects regression is shown.