3.1 Participants and Clinical Outcomes
Out of 44 individuals initially considered suitable for the study, 5 were later excluded due to refusal to undergo the baseline MRI (2 participants) or the 6-month MRI scans (3 participants). In the end, we managed to include 39 individuals in the concluding analysis (see Figure 1). Among the 39 individuals, the median age was 28 years (IQR: 22 to 37.5), with 59% being male. Additionally, 61.5% had diabetes or prediabetes, and 84.6% were diagnosed with MAFLD. The medians (IQRs) or means ± SDs of baseline weight, BMI, WC, fasting glucose, FINS, HOMA-IR, and HOMA-β were 88.8 ± 13.4 kg, 30.4 (4.7) kg/m2, 99.0 (7.5) cm2, 5.7 ± 0.7 mmol/L, 23.7 (9.3) uU/ml, 6.2 (2.8) and 241.1 (161.7), respectively. After lifestyle intervention of six months, weight dropped to 80.8 ± 13.7 kg, BMI was 28.3 (4.4) kg/m2, waist circumference measured 92.9 (9.6) cm2, fasting glucose levels were 5.2 ± 0.6 mmol/L, fasting insulin was 12.6 (7.1) uU/ml, HOMA-IR at 2.9 (1.8), and HOMA-β was 161.6 (145.9), with all reductions being statistically significant (P < 0.05). Table 1 provides a summary of all baseline and post-intervention anthropometric and laboratory data.
Figure 1. Flowchart of patient enrollment.
Table 1. Anthropometric and lab measurements before and after lifestyle intervention.
|
Baseline
|
6 months
|
P value
|
n
|
39
|
age, median (IQR)
|
28.0 (15.5)
|
gender, n (%)
|
|
female
|
16 (41.0%)
|
male
|
23 (59.0%)
|
glucometabolic states
|
39
|
0.31
|
diabetes
|
5
|
4
|
prediabetes
|
19
|
13
|
normal glucose tolerance
|
15
|
22
|
MAFLD
|
33
|
22
|
0.006
|
Weight, mean ± SD, kg
|
88.8 ± 13.4
|
80.8 ± 13.7
|
< 0.001
|
BMI, median (IQR)
|
30.4 (4.7)
|
28.3 (4.4)
|
< 0.001
|
WC, median (IQR), cm
|
99.0 (7.5)
|
92.9 (9.6)
|
< 0.001
|
HC, median (IQR), cm
|
103.5 (6.5)
|
97.9 (7.2)
|
< 0.001
|
WHR, mean ± SD
|
0.97 ± 0.05
|
0.96 ± 0.06
|
0.32
|
SBP, mean ± SD, mmHg
|
126.7 ± 9.3
|
118.6 ± 7.7
|
< 0.001
|
DBP, median (IQR), mmHg
|
73.0 (14)
|
70.0 (11)
|
< 0.001
|
TG, median (IQR)
|
2.3 (1.0)
|
1.1 (0.4)
|
< 0.001
|
LDL-C, mean ± SD
|
2.9 ± 0.8
|
2.9 ± 0.7
|
0.96
|
TC, mean ± SD
|
5.2 ± 0.8
|
4.6 ± 0.9
|
0.006
|
HDL-C, median (IQR)
|
0.96 (0.27)
|
1.16 (0.34)
|
0.010
|
UA, median (IQR)
|
436 (76.5)
|
349 (178)
|
0.04
|
ALT, median (IQR)
|
36.0 (29.5)
|
19.0 (21.0)
|
0.009
|
AST, mean ± SD
|
34.9 ± 17.4
|
22.4 ± 9.3
|
0.004
|
TBIL, median (IQR)
|
10.6 (6.1)
|
11.2 (7.8)
|
0.47
|
DBIL, median (IQR)
|
3.2 (1.5)
|
3.8 (3.6)
|
0.05
|
Crea, mean ± SD
|
69.0 ± 14.6
|
64.2 ± 14.1
|
0.297
|
Glu0, mean ± SD
|
5.7 ± 0.7
|
5.2 ± 0.6
|
0.005
|
FINS, median (IQR)
|
23.7 (9.3)
|
12.6 (7.1)
|
<0.001
|
Glu30, mean ± SD
|
10.0 ± 1.93
|
9.2 ± 1.6
|
0.13
|
Glu60, median (IQR)
|
10.3 (4.8)
|
9.7 (2.8)
|
0.27
|
Glu120, median (IQR)
|
8.0 (3.8)
|
7.1 (3.5)
|
0.23
|
HbA1c%, mean ± SD
|
5.8 ± 0.3
|
5.6 ± 0.4
|
0.16
|
HOMA-IR, median (IQR)
|
6.2 (2.8)
|
2.9 (1.8)
|
< 0.001
|
HOMA-β(%), median (IQR)
|
241.1 (161.7)
|
161.6 (145.9)
|
0.0001
|
△I30/△G30, median (IQR)
|
16.8 (31.4)
|
29.6 (29.3)
|
0.20
|
AUCI60-120/G60-120, median (IQR)
|
17.9 (14.7)
|
12.1 (5.8)
|
0.33
|
ISI, median (IQR)
|
23.3 (12.2)
|
51.2 (27.2)
|
0
|
DI60-120, median (IQR)
|
569.9 (295.0)
|
576.2 (232.0)
|
0.32
|
SFA, median (IQR)
|
229.1(118.2)
|
205.1 (118.4)
|
<0.001
|
VFA, median (IQR)
|
109.0 (28.2)
|
92.1 (47.8)
|
<0.001
|
Hepatic PDFF, median (IQR)
|
14.6 (15.1)
|
8.1 (8.5)
|
<0.001
|
Pancreatic PDFF, median (IQR)
|
9.6 (7.6)
|
6.7 (6.9)
|
<0.001
|
Abbreviations: IQR, interquartile range; MAFLD, metabolically associated fatty liver disease; BMI, body mass index; WC, waist circumference; HC, hip circumference;WHR, waist-to-hip ratio, SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; LDL-C, low-density lipoprotein cholesterol; TC, total cholesterol; HDL-C stands for high-density lipoprotein cholesterol; UA, uric acid; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TBIL, total bilirubin; DBIL, direct bilirubin; Crea, creatinine; FINS, fasting insulin; HbA1c, glycated hemoglobin;HOMA-IR, an index for evaluating insulin resistance through the homeostatic model; HOMA-β, homeostatic model assessment of β-cell function; △I30/△G30, the first phase of insulin response to glucose challenge; AUCI60-120/G60-120, late insulin secretion to glucose challenge; ISI, insulin sensitivity index; DI60-120, late insulin secretion; PDFF, proton density fat fraction; VFA, visceral fat area; SFA, subcutaneous fat area.
The baseline SFA, VFA, hepatic PDFF and pancreatic PDFF were 229.1 (193.5--311.7) cm2, 109.0 (102.6--130.8) cm2, 14.6 (9.6--24.7)%, and 9.6 (6.6--14.2)%, respectively. After lifestyle intervention of six months, the subcutaneous fat area reduced to 205.1 (168.4–286.8) cm2, the visceral fat area dropped to 92.1 (70.3–118.0) cm2, the liver proton density fat fraction decreased to 8.1 (3.0–11.5)%, and the pancreatic PDFF fell to 6.7 (3.4–10.3)%; all these declines were statistical significance (P < 0.001). Figure 2 illustrates the decreases in abdominal fat and intraorgan PDFF caused by the treatment.
Figure 2. Effect of 6 months lifestyle intervention on mobilization of fat storage pools. (a) changes in hepatic proton density fat fraction (PDFF); (b) changes in pancreatic PDFF; (c) changes in subcutaneous fat area; and (d) changes in visceral fat area.
After lifestyle intervention of six months, hepatic PDFF saw the highest reduction at 46.5% (28.8%-68.4%), with pancreatic PDFF decreasing by 24.9% (10.4%-45.0%), VFA by 19.5% (7.2%-32.3%), and SFA by 12.2% (6.7%-18.9%) (P <0.001). Figure 3a. shows the treatment-caused varying mobilization of specific body fat areas. A typical example of site-specific fat mobilization after lifestyle intervention is shown in Figure 3 b-d.
Figure 3. Changes in specific body fat areas from the baseline to six months after lifestyle intervention. (a) Comparative analysis of percentage reductions in localized body fat deposits. (b)-(d) A typical example of site-specific fat mobilization after lifestyle intervention (21 years, female, and BMI 30.8 kg/m2). (b) Decrease in belly fat area due to treatment. The visceral fat area (VFA) is highlighted in red, while the subcutaneous fat area (SFA) is marked in green. (c) Decrease in liver proton density fat fraction (PDFF) due to treatment. (d) Decrease in pancreatic PDFF due to treatment. ROI, region of interest.
Furthermore, an analysis of subgroups categorized by gender, body mass index, and glycometabolic status also showed comparable variations in fat mobilization (see Supplemental Fig.S1-3).
3.2 Relationships between localized fat reduction and metabolic indicator
Table 2 provides a summary of the Pearson correlation coefficients for changes in weight, BMI, waist circumference, hip circumference, waist-to-hip ratio, subcutaneous fat area, visceral fat area, and pancreatic PDFF; hepatic PDFF; as well as fasting plasma glucose, fasting plasma insulin, HOMA-IR, HOMA-β, ISI, triglycerides, LDL-C, HDL-C, systolic blood pressure, and diastolic blood pressure. The observed positive relationships included: changes in weight and LDL-C (r = 0.432, P = 0.01), changes in BMI and LDL-C (r = 0.385, P = 0.03), changes in VFA and glucose (r = 0.401, P = 0.01), changes in VFA and HOMA-IR (r = 0.830, P < 0.001), changes in VFA and TG (r = 0.688, P = 0), changes in hepatic PDFF and HOMA-IR (r = 0.520, P < 0.001), changes in hepatic PDFF and TG (r = 0.630, P < 0.001), and changes in pancreatic PDFF and LDL-C (r = 0.409, P = 0.02).
Table 2. Relationships between specific fat reduction and metabolic indicator.
Pearson correlation
|
△FPG
|
△insulin
|
△HOMA-IR
|
△HOMA-β
|
△ISI
|
△TG
|
△LDL-C
|
△HDL-C
|
△SBP
|
△DBP
|
△Weight
|
-0.015
|
-0.238
|
-0.134
|
-0.023
|
-0.044
|
-0.106
|
0.432*
|
-0.001
|
0.084
|
0.264
|
△BMI
|
-0.019
|
-0.218
|
-0.144
|
-0.010
|
-0.083
|
-0.050
|
0.385*
|
-0.040
|
0.010
|
0.200
|
△WC
|
-0.235
|
-0.115
|
-0.405
|
0.100
|
0.078
|
-0.452
|
0.177
|
0.157
|
0.086
|
0.137
|
△HC
|
-0.122
|
-0.171
|
-0.419
|
0.032
|
0.383
|
-0.149
|
0.090
|
0.201
|
0.236
|
-0.083
|
△WHR
|
-0.165
|
0.017
|
-0.061
|
0.053
|
-0.144
|
-0.305
|
0.046
|
0.041
|
-0.031
|
0.255
|
△SFA
|
-0.274
|
0.332
|
0.101
|
0.306
|
0.061
|
0.144
|
0.057
|
0.045
|
0.023
|
0.306
|
△VFA
|
0.401*
|
0.177
|
0.830**
|
-0.215
|
-0.272
|
0.688*
|
-0.312
|
-0.177
|
-0.119
|
0.226
|
△Pancreatic PDFF
|
-0.139
|
0.030
|
-0.284
|
0.210
|
-0.172
|
-0.215
|
0.409*
|
-0.178
|
0.106
|
-0.093
|
△Hepatic PDFF
|
0.206
|
0.174
|
0.520**
|
-0.073
|
0.077
|
0.630**
|
-0.164
|
-0.129
|
-0.211
|
-0.004
|
Abbreviations: BMI (body mass index), WC (waist circumference), HC (hip circumference), WHR (waist-to-hip ratio), SFA (subcutaneous fat area), VFA (visceral fat area), PDFF (proton density fat fraction), FPG (fasting plasma glucose), HOMA-IR (homeostatic model assessment of insulin resistance), HOMA-β (homeostatic model assessment of β-cell function), ISI (insulin sensitivity index), TG (triglycerides), LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), SBP (systolic blood pressure), DBP (diastolic blood pressure).