Baseline characteristics of study population:
As described in our previous study [25], 260 patients were enrolled between January 2013 and Oct 2018 into the milk-based meal replacement programme at the Bariatric Medicine clinic in Galway University Hospitals. Of these, 139 (53.5%) completed all 24 weeks of the intervention, with 121 (46.5%) discontinuing the intervention. From 139 completers, 105 (75.5%) agreed to participate in this study and provided written informed consent. Given that 1867 new patients were seen in our bariatric service over the six-year study period, 13.9% of newly referred bariatric patients ultimately participated in our milk programme.
Details of patients’ characteristics are shown in Table 1. The average age of participants was 51.1 ± 11.2 (range 18.0-71.6) years. 56 (53.3%) were female. The overall median baseline ALT level was 28.0 [20.0, 40.5] iu/l. The 48 patients with a high ALT had no statistically significant differences to the 57 with normal ALT in age, sex, anthropometric or metabolic variables.
Table 1
Baseline characteristics of patients completing the milk programme
Parameters
|
All patients
|
Normal ALT
|
High ALT
|
P
|
N (%)
|
105 (100%)
|
57 (54.3%)
|
48 (45.7%)
|
|
Female
|
56 (53.3 %)
|
33 (57.9 %)
|
23 (47.9 %)
|
0.307
|
Age (years)
|
51.1±11.2
|
52.9±9.4
|
49.1±12.8
|
0.079
|
Height (m)
|
1.7±0.1
|
1.7±0.1
|
1.7±0.1
|
0.502
|
Weight (kg)
|
144.0±27.6
|
145.2±27.3
|
142.6±28.2
|
0.627
|
BMI (kg m2)
|
50.6±8.0
|
51.5±8.2
|
49.7±8.0
|
0.254
|
EBW%
|
102.5±32.0
|
106.0±33.0
|
98.6±31.2
|
0.254
|
ALT* (iu/l)
|
28.0 [20.0,40.5]
|
22.0 [17.0,24.5]
|
41.5 [34.3,63.5]
|
<0.0005
|
Total cholesterol (mmol/l)
|
4.6±1.0
|
4.6±1.0
|
4.6±1.0
|
0.786
|
LDL (mmol/l)
|
2.5±0.9
|
2.5±0.9
|
2.6±0.8
|
0.442
|
HDL (mmol/l)
|
1.2±0.4
|
1.3±0.4
|
1.2±0.4
|
0.131
|
Triglyceride (mmol/l)
|
1.8±0.8
|
1.7±0.6
|
1.9±1.0
|
0.151
|
Diabetes
|
37 (35.2 %)
|
19 (33.3 %)
|
18 (37.5 %)
|
0.656
|
HbA1c (mmol/mol)
|
48.2±15.6
|
48.1±16.3
|
48.4±15.0
|
0.943
|
Medications
|
|
|
|
|
Metformin
|
38 (36.2 %)
|
22 (38.6 %)
|
16 (33.3 %)
|
0.576
|
Insulin
|
10 (9.5 %)
|
7 (12.3 %)
|
3 (6.3 %)
|
0.294
|
SU
|
15 (14.3 %)
|
10 (17.5 %)
|
5 (10.4 %)
|
0.298
|
DPP4
|
9 (8.6 %)
|
6 (10.5 %)
|
3 (6.3 %)
|
0.436
|
SGLT2
|
6 (5.7 %)
|
3 (5.3 %)
|
3 (6.3 %)
|
0.828
|
GLP1
|
18 (17.1 %)
|
9 (15.8 %)
|
9 (18.8 %)
|
0.688
|
PPARG
|
1 (1 %)
|
1 (1.8 %)
|
-
|
0.356
|
ARBs
|
25 (23.8 %)
|
12 (21.1 %)
|
13 (27.1 %)
|
0.470
|
ACEIs
|
30 (28.6 %)
|
19 (33.3 %)
|
11 (22.9 %)
|
0.239
|
Beta Blockers
|
31 (29.5 %)
|
17 (29.8 %)
|
14(29.2 %)
|
0.914
|
Alpha blockers
|
6 (5.7 %)
|
3 (5.3 %)
|
3 (6.3 %)
|
0.828
|
Diuretics
|
31 (29.5 %)
|
15 (26.3 %)
|
16 (33.3 %)
|
0.432
|
Ezetemibe
|
4 (3.8 %)
|
2 (3.4 %)
|
2 (4.2 %)
|
0.861
|
Values are presented as Mean ± SD.
|
*Denotes variables that are not normally distributed presented as median [IQR].
|
Comparisons between groups were made using Independent samples t-test for normally distributed data, and Mann-Whitney U test for non-normally distributed data.
|
Proportions with categorical variables were compared using Pearson’s Chi-square test.
|
BMI= Body Mass Index, EBW%= Excess Body Weight Percentage, ALT= Alanine Aminotransferase, LDL= Low Density Lipoprotein, HDL= High Density Lipoprotein, HbA1c= Glycated haemoglobin, SU= Sulfonylureas, DDP4= Dipeptidyl peptidase-4 inhibitors, SGLT2= Sodium-glucose co-transporter 2 inhibitors, GLP1= Glucagon-like peptide 1, PPARG= Peroxisome proliferator-activated receptor gamma, ARBs= Angiotensin II receptor blockers and ACEIs= Angiotensin-converting enzyme inhibitors.
|
Changes in ALT, anthropometrics, and metabolic variables over 24 weeks:
Table 2 describes the changes in anthropometric variables and ALT levels at weeks 2, 4, 6, 8, 16, and 24 of the programme. From baseline to week 2, ALT levels significantly increased from 28.0 [20.0, 40.5] iu/l to 40.0 [26.0, 55.0] iu/l (p < 0.0005), while from baseline to week 24, there was a statistically significant overall reduction in ALT from 28.0 [20.0, 40.5] iu/l to 21.0 [17.0, 28.3] iu/l (p < 0.0005). Over time ALT increased from a baseline value of 25 [20.0, 37.3] iu/l to 38 [26.0, 53.5], and 39 [26.0, 60.0] iu/l in weeks 2 and 4, respectively, followed by a significant subsequent reduction to 35 [26.0, 49.0], 32 [23.0, 41.3], 24 [19.0, 34.3], and 21 [17.0, 28.3] iu/l (p < 0.0005) at weeks 6, 8, 16, and 24, respectively (Table 2; Fig. 1a). When we compared patients with normal versus high baseline ALT levels we found that the rise in ALT was greater in those with high baseline ALT, in whom ALT rose from 41.5 [34.3, 63.5] iu/l to 51.0 [41.0,78.0] iu/l (p = 0.001) at week 2, then decreased to 27.0 [21.0, 33.5] iu/l (p < 0.0005) by 24 weeks. Taking a slightly different analytical approach and using the Friedman test (the non-parametric equivalent of analysis of variance), similar results were obtained with ALT increasing from 41.0 [33.0, 62.5] iu/l at baseline to 50.0 [40.5, 85.0], and 50.5 [39.5, 68.3] iu/l at weeks 2, and 4, respectively, reaching 27.0 [21.0, 33.5] iu/l (p < 0.0005) by 24 weeks. In contrast, those with normal baseline ALT levels had a non-significant increase in ALT from 20.5 [17.0, 24.0] iu/l to 29.5 [20.3, 41.0] iu/l at week 2, followed by a subsequent reduction to 19.0 [16.0, 22.0] iu/l, (p < 0.0005) by 24 weeks (Table 2; Fig. 1b). As described in this cohort previously [25], there were significant reductions in HbA1c in patients with and without type 2 diabetes (Table 2).
Table 2
Changes in anthropometric and metabolic variables over time in patients with normal and high baseline ALT completing the milk programme.
Parameters | Week 0 | Week 2 | Week 4 | Week 6 | Week 8 | Week 16 | Week 24 | p |
ALT (iu/l)* | 25 [20.0,37.3] | 38 [26.0,53.5] | 39 [26.0,60.0] | 35 [26.0,49.0] | 32 [23.0,41.3] | 24 [19.0,34.3] | 21 [17.0,28.3] | < 0.0005 |
ALT (iu/l)*Δ | 41.0 [33.0,62.5] | 50.0 [40.5,85.0] | 50.5 [39.5,68.3] | 41.0 [34.0,67.3] | 39.0 [32.0,51.0] | 34.5 [25.0,41.3] | 26.5 [21.0,36.5] | < 0.0005 |
ALT normal (iu/l)*# | 20.5 [17.0,24.0] | 29.5 [20.3,41.0] | 28.5 [20.3,43.0] | 27.0 [21.3,38.5] | 26.0 [18.3,36.0] | 20.0 [17.0,25.0] | 19.0 [16.0,22.0] | < 0.0005 |
Weight (kg) | 144.2 ± 28.0 | 137.6 ± 27.4 | 134.1 ± 27.0 | 131.0 ± 26.2 | 128.3 ± 25.6 | 123.0 ± 25.0 | 121.6 ± 25.4 | < 0.0005 |
BMI (kg m2) | 50.7 ± 8.1 | 47.4 ± 10.4 | 45.4 ± 12.0 | 44.5 ± 12.0 | 45.2 ± 7.6 | 43.2 ± 7.5 | 43.0 ± 7.6 | < 0.0005 |
EBW (%) | 103.1 ± 32.4 | 89.6 ± 42.0 | 81.6 ± 48.2 | 78.3 ± 47.4 | 81.0 ± 30.6 | 73.0 ± 30.0 | 71.0 ± 31.0 | < 0.0005 |
HbA1c (mmol/mol)† | 39.3 ± 4.0 | 37.6 ± 4.0 | 37.0 ± 4.0 | 36.3 ± 4.0 | 36.0 ± 4.2 | 35.4 ± 3.3 | 35.3 ± 3.5 | < 0.0005 |
HbA1c (mmol/mol)‡ | 67.2 ± 13.3 | 62.2 ± 13.0 | 59.0 ± 13.0 | 56.0 ± 14.2 | 54.0 ± 15.0 | 48.5 ± 14.4 | 48.6 ± 14.1 | < 0.0005 |
LDL (mmol/l) | 2.6 ± 1.0 | 2.2 ± 1.0 | 2.1 ± 0.7 | 2.2 ± 1.0 | 2.2 ± 1.0 | 2.5 ± 1.0 | 2.6 ± 1.0 | < 0.0005 |
HDL (mmol/l) | 1.2 ± 0.4 | 1.1 ± 0.3 | 1.1 ± 0.3 | 1.1 ± 0.3 | 1.1 ± 0.3 | 1.2 ± 0.3 | 1.3 ± 0.4 | < 0.0005 |
Triglyceride (mmol/l) | 1.8 ± 0.7 | 1.5 ± 0.6 | 1.4 ± 0.5 | 1.4 ± 0.5 | 1.3 ± 0.5 | 1.3 ± 0.5 | 1.3 ± 0.5 | < 0.0005 |
Total cholesterol (mmol/l) | 4.6 ± 1.0 | 3.9 ± 1.0 | 3.7 ± 1.0 | 3.8 ± 1.0 | 4.0 ± 1.0 | 4.2 ± 1.0 | 4.4 ± 1.0 | < 0.0005 |
Values are presented as Mean ± SD. |
*Denotes variables that are not normally distributed presented as median [IQR]. |
Δ Denotes variables that represent values higher than normal at the start of the programme. |
# Denotes variables that represent values that were normal at the start of the programme. |
† Denote patients without history of type 2 diabetes. ‡Denote patients with history of type 2 diabetes. |