Table 2 Changes in traits after lifestyle intervention in Danish children and adolescents with and without damaging MC4R mutations.

	Children with damaging or unresolved MC4R mutations (group A)		Children with benign or no MC4R mutations (group B)		p for difference of mean delta change between groups A and B^a
	n	Mean delta change (SD)	n	Mean delta change (SD)		Adjusted for BMI change
BMI SDS	24	−0.033 (0.45)	982	−0.27 (0.43)	0.005	–
Height-for-age SDS	24	−0.097 (0.21)	982	−0.025 (0.29)	0.38	0.44
FFMI, kg/m² (log)	13	0.081 (0.067)	555	0.049 (0.063)	0.15	0.41
BFMI, kg/m² (log)	13	0.11 (0.23)	555	−0.041 (0.21)	0.13	0.73
BMD, g/cm² (log)	13	0.035 (0.046)	555	0.041 (0.059)	0.090	0.057
SBP SDS	19	−0.44 (0.94)	792	−0.16 (1.06)	0.19	0.080
DBP SDS	19	0.17 (0.87)	792	−0.20 (0.84)	0.39	0.72
Glucose, mmol/l	8	−0.1 (0.53)	549	0.041 (0.66)	0.82	0.84
HbA1c, mmol/mol^b	11	−0.18 (2.18)	581	−0.29 (2.30)	1.00	0.87
Insulin, pmol/l (log)	12	0.11 (0.65)	569	−0.22 (0.67)	0.18	0.50
TSH, mU/l^b (log)	11	−0.21 (0.52)	589	−0.10 (0.42)	0.72	0.79
T3, nmol/l	10	0.005 (0.27)	461	−0.041 (0.36)	0.79	0.55
T4, pmol/l^b	11	−0.045 (2.90)	585	−0.84 (2.29)	0.69	0.56
Total cholesterol, mmol/l^b	11	−0.21 (0.76)	577	−0.066 (0.60)	0.72	0.55
HDL cholesterol, mmol/l	11	−0.11 (0.19)	579	0.047 (0.22)	0.017	0.050
LDL cholesterol, mmol/l^b	11	−0.18 (0.71)	576	−0.11 (0.53)	0.97	0.77
Triglycerides, mmol/l^b (log)	11	0.13 (0.77)	576	−0.0074 (0.46)	0.24	0.44

When analyzing the lifestyle intervention response outcomes, mean and standard deviation with respect to change from baseline (delta change) were calculated for each group. We then assessed the difference between the mean values between groups A and B (hence comparing differences-in-differences). p values in bold indicate p < 0.05.
MC4R Melanocortin-4 Receptor, CI confidence interval, BMI body mass index, SDS standard deviation score, SBP systolic blood pressure, DBP diastolic blood pressure, FFMI fat-free mass index, BFMI body fat mass index, TSH thyroid-stimulating hormone, HDL high-density lipoprotein, LDL low-density lipoprotein.
^aData were analyzed with a multiple regression analysis adjusted for age, sex, pubertal status, baseline value of the respective trait, follow-up time, and type of DXA scanner (where appropriate). We also present all significance results from analyses with additional adjustment for BMI change.
^bOutliers excluded prior to analyses (n = 1 in group B for T4, total cholesterol, LDL cholesterol, and triglycerides; n = 2 in group B for HbA1c and TSH).

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